Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
April-2026 Volume 57 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2026 Volume 57 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review)

  • Authors:
    • Wei Li
    • Wen-Hong Wang
    • Yi Song
    • Xu-Jiong Li
    • Yan Li
    • Xia Wang
    • Ting-Ting Tian
    • Xiao Huang
    • Li Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Exercise Physiology, Beijing Sport University, Beijing 100084, P.R. China, Key Laboratory of Bone Biomaterials and Dong Medicine‑Regulated Organoid Regeneration of Hunan Provincial Universities, Biomedical Research Institute, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, Department of Neurosurgery, Chongqing University Three Gorges Hospital, Chongqing 404100, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 84
    |
    Published online on: February 4, 2026
       https://doi.org/10.3892/ijmm.2026.5755
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive decline and whose pathology is closely linked to cellular autophagy dysfunction. Autophagy is a key process involved in cell clearance. Impaired autophagy can drive neuronal damage and death related to AD pathology. Therefore, targeting autophagy dysfunction has emerged as a promising therapeutic strategy. Exercise, as a non‑pharmaceutical and low‑cost intervention method, can enhance autophagy activity and alleviate AD symptoms. However, the mechanism by which it regulates autophagy in AD remains unclear. The present review summarizes evidence that exercise acts as an effective early intervention. Exercise activates key cellular signaling pathways (mammalian target of rapamycin, sirtuin 1 and adiponectin receptor 1) and regulates microRNAs (small non‑coding RNAs) and irisin (a muscle hormone) to restore normal autophagy. The present review also explores the use of exercise combined with natural products for potential synergistic therapeutic effects. This review provides insights into developing new AD prevention and management strategies by detailing how exercise corrects AD‑related autophagy dysfunction.

View Figures

Figure 1

Overview of autophagy pathways. (A)
The three types of autophagy. Macroautophagy is initiated by the
ULK complex (comprising ULK1, ATG13, ATG101, and FIP200), with
phagophore nucleation and elongation driven by the VPS34 complex
(beclin-1, ATG14L, VPS34 and VPS15) and the ATG5-ATG12-ATG16L
complex. During this process, LC3 is covalently conjugated with PE
to form membrane-associated LC3-II, a hallmark of maturing
autophagosomes, which subsequently fuse with lysosomes to generate
autolysosomes where luminal hydrolases degrade sequestered
cytoplasmic cargo. Microautophagy entails the direct invagination
of lysosomal membranes to engulf cytosolic components without the
formation of an autophagosome intermediate, facilitating direct
degradation. Chaperone-mediated autophagy, a selective degradative
pathway, relies on cytosolic HSC70 to recognize target proteins
bearing the KFERQ motif, which are then translocated into the
lysosomal lumen via the lysosomal membrane protein LAMP2A for
targeted proteolysis. (B) Three forms of selective autophagy and
cargo receptors. Selective autophagy specifically targets distinct
cytoplasmic cargoes, including protein aggregates, mitochondria and
peroxisomes, through a repertoire of autophagy receptors (for
example, p62, NDP52, OPTN, NBR1 and TAX1BP1) that harbor a UBD for
binding Ub cargo and a LIR to anchor the receptor-cargo complex to
LC3 on the autophagosomal membrane, thereby enabling the selective
sequestration and degradation of damaged organelles or toxic
protein aggregates by the autophagic machinery. ATG5,
autophagy-associated protein 5; ATG12, autophagy-associated protein
12; ATG13, autophagy-associated protein 13; ATG14L,
autophagy-associated protein 14L; ATG16L, autophagy-associated
protein 16L; FIP 200, FAK family-interacting protein of 200 kDa;
HSC70, heat shock cognate 70-kDa protein; LC3,
microtubule-associated protein 1 light chain 3; LC3-II,
microtubule-associated protein 1 light chain 3-II; LAMP2A,
lysosomal-associated membrane protein 2A; KFERQ, Kex2-Fer1-Endo
U1-Qc-2 motif; NBR1, next to BRCA1 gene 1; NDP52, nuclear dot
protein 52; OPTN, optineurin; p62, sequestosome 1; PE,
phosphatidylethanolamine; TAX1BP1, tax1 (human T-cell leukemia
virus type I) binding protein 1; UBD, ubiquitin-binding domain; Ub,
ubiquitinated; LIR, LC3 interaction region; ULK, UNC 51-like
kinase; ULK1, UNC 51-like kinase 1; VPS15, vesicular protein
sorting 15; VPS34, vesicular protein sorting 34.

Figure 2

Signaling pathways behind the
exercise regulation of autophagy dysfunction in AD. (A) Exercise
activates the PI3K/AKT signaling cascade, which subsequently
activates GSK-3β to modulate Tau protein phosphorylation.
Simultaneously, exercise elevates the cellular AMP/ATP ratio,
triggering AMPK activation. Activated AMPK then inhibits mTORC1
through the TSC1/2-Rheb signaling cascade, upregulates VMA21
expression and activates ULK1. Collectively, these events augment
autophagic flux and reduce Aβ oligomer accumulation. (B) Exercise
activates the AdipoR1-AMPK-SIRT1 signaling axis, which upregulates
PGC-1α to suppress BACE1 and ADAM-10, thus reducing APP processing
and Aβ production. Concomitantly, SIRT1 modulates FOXO1/3 to
activate PINK1/Parkin-mediated mitophagy, while upregulating
Beclin-1, ULK1, LAMP1 and cathepsin D to enhance autophagic
degradation. Furthermore, exercise upregulates TFEB and PGC-1α,
which coordinately promote autophagy and mitochondrial biogenesis,
and activates Nrf2 to mitigate ROS accumulation, ultimately
ameliorating cognitive decline and core pathological hallmarks of
AD by restoring autophagic and mitochondrial homeostasis. Red
arrows represent upregulation, while green arrows represent
downregulation. Black arrows indicate promotion and red lines with
a line across represent inhibition. AD, Alzheimer's disease; Aβ,
amyloid β-protein; APP, amyloid precursor protein; AdipoR1,
adiponectin receptor 1; ADAM-10, a disintegrin and metalloprotease
10; AKT, protein kinase B; AMP, adenosine monophosphate; AMPK,
AMP-activated protein kinase; ATP, adenosine triphosphate; BACE-1,
β-secretase 1; FOXO1/3, forkhead box O1/3; GSK-3β, glycogen
synthase kinase-3β; LAMP1, lysosomal-associated membrane protein 1;
mTORC1, mammalian target of rapamycin complex 1; Nrf2, nuclear
factor erythroid 2-related factor 2; Tau, microtubule-associated
protein tau; PI3K, phosphatidylinositol 3-kinase; PINK1,
PTEN-induced kinase 1; Parkin, parkin E3 ubiquitin ligase; PGC-1α,
PPARγ coactivator-1α; Raptor, a core component of mTORC1; Rheb, ras
homolog enriched in brain; ROS, reactive oxygen species; SIRT1,
sirtuin 1; TFEB, transcription factor EB; TSC2, tuberous sclerosis
complex 2; TSC1, tuberous sclerosis complex 1; ULK1, UNC 51-like
kinase 1; VMA21, vacuolar ATPase assembly factor VMA21.

Figure 3

Exercise regulates autophagy through
miRNA-mediated mechanisms. Exercise modulates several crucial
miRNAs, such as miR-130a, miR-331-3p, miR-9-5p and miR-34a.
Specifically, miR-130a activates AMPK, which subsequently
upregulates ATG7, p62 and the LC3-II/LC3-I ratio, thereby enhancing
autophagic flux. miR-331-3p increases the expression of p62 and
OPTN, thereby promoting autophagic flux. Meanwhile, miR-9-5p and
miR-34a work together to upregulate SIRT1 and downregulate mTOR.
SIRT1 enhances mitophagy, which suppresses ROS generation, while
mTOR inhibition further boosts autophagic flux. Enhancing both
autophagy and mitophagy significantly reduces Aβ plaque deposition,
mitigates neuroinflammation, improves synaptic plasticity and
inhibits neuronal death. This combined effect ultimately leads to a
marked improvement in cognitive function within AD-related
pathological contexts. Red arrows represent upregulation, while
green arrows represent downregulation. Black arrows indicate
promotion and red lines with a line across represent inhibition.
Aβ, amyloid β-protein; AMPK, adenosine monophosphate-activated
protein kinase; ATG7, autophagy-associated protein 7; LC3-II,
microtubule-associated protein 1 light chain 3-II; LC3-I,
microtubule-associated protein 1 light chain 3-I; mTOR, mammalian
target of rapamycin; miR/miRNA, microRNA; OPTN, optineurin; p62,
sequestosome 1; ROS, reactive oxygen species; SIRT1, sirtuin 1.

Figure 4

Irisin is involved in the regulation
of autophagy. Physical exercise stimulates the release of irisin,
which specifically targets astrocytes and neurons in the
hippocampus of brains affected by AD. In astrocytes, irisin
activates the ERK-STAT3 signaling pathway, promoting the secretion
of NEP, an essential enzyme for degrading Aβ. In neurons, irisin
binds to cell-surface receptors and activates AMPK, which inhibits
the mTOR pathway. This inhibition enhances autophagic flux,
facilitating the degradation of Aβ oligomers and thereby reducing
Aβ plaque burden. Irisin-driven mechanisms in astrocytes and
neurons collaboratively alleviate Aβ-related pathology in the AD
hippocampus. This positions irisin as a key molecular connection
among physical exercise, autophagy regulation and the mitigation of
AD pathological features. Aβ, amyloid β-protein; AMPK, adenosine
monophosphate-activated protein kinase; ERK, extracellular
signal-regulated kinase; mTOR, mammalian target of rapamycin; NEP,
enkephalin; STAT3, signal transducer and activator of transcription
3.

Figure 5

A visual summary of the core content
of the present review. In patients with AD and preclinical models
of AD, autophagy dysfunction in hippocampal neurons leads to the
accumulation of Aβ plaques and neurofibrillary tangles, resulting
in severe memory and cognitive impairments. Exercise intervention
modulates key molecular regulators, such as mTOR, SIRT1, AdipoR1
and microRNAs, to enhance autophagic flux in the hippocampus. This
process alleviates the pathological burden of Aβ plaques and
neurofibrillary tangles, consequently restoring impaired memory and
cognitive function. Additionally, the combination of exercise and
natural products significantly potentiates the favorable regulatory
effects on autophagic flux, enhancing autophagy-mediated
neuroprotective outcomes in AD. AD, Alzheimer's disease; mTOR,
mammalian target of rapamycin; SIRT1, sirtuin 1; AdipoR1,
adiponectin receptor 1.
View References

1 

Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J and van der Flier WM: Alzheimer's disease. Lancet. 397:1577–1590. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Reitz C, Pericak-Vance MA, Foroud T and Mayeux R: A global view of the genetic basis of Alzheimer disease. Nat Rev Neurol. 19:261–277. 2023. View Article : Google Scholar : PubMed/NCBI

3 

Di Meco A, Curtis ME, Lauretti E and Praticò D: Autophagy dysfunction in Alzheimer's Disease: Mechanistic insights and new therapeutic opportunities. Biol Psychiatry. 87:797–807. 2020. View Article : Google Scholar

4 

Hardy J and Selkoe DJ: The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science. 297:353–356. 2002. View Article : Google Scholar : PubMed/NCBI

5 

De Strooper B and Karran E: The cellular phase of Alzheimer's disease. Cell. 164:603–615. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Iqbal K, Liu F and Gong CX: Tau and neurodegenerative disease: The story so far. Nat Rev Neurol. 12:15–27. 2016. View Article : Google Scholar

7 

Tong BC, Wu AJ, Huang AS, Dong R, Malampati S, Iyaswamy A, Krishnamoorthi S, Sreenivasmurthy SG, Zhu Z, Su C, et al: Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease. Autophagy. 18:624–642. 2022. View Article : Google Scholar :

8 

Nixon RA: Autophagy-lysosomal-associated neuronal death in neurodegenerative disease. Acta Neuropathol. 148:422024. View Article : Google Scholar : PubMed/NCBI

9 

Tzioras M, McGeachan RI, Durrant CS and Spires-Jones TL: Synaptic degeneration in Alzheimer disease. Nat Rev Neurol. 19:19–38. 2023. View Article : Google Scholar

10 

Butterfield DA and Halliwell B: Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci. 20:148–160. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Deng Z, Dong Y, Zhou X, Lu JH and Yue Z: Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles. Acta Pharm Sin B. 12:1688–1706. 2022. View Article : Google Scholar : PubMed/NCBI

12 

Lee JH and Nixon RA: Autolysosomal acidification failure as a primary driver of Alzheimer disease pathogenesis. Autophagy. 18:2763–2764. 2022. View Article : Google Scholar : PubMed/NCBI

13 

Rubinsztein DC, Codogno P and Levine B: Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov. 11:709–730. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Levine B and Kroemer G: Biological functions of autophagy genes: A disease perspective. Cell. 176:11–42. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Yu L, Chen Y and Tooze SA: Autophagy pathway: Cellular and molecular mechanisms. Autophagy. 14:207–215. 2018. View Article : Google Scholar :

16 

Kaushik S, Tasset I, Arias E, Pampliega O, Wong E, Martinez-Vicente M and Cuervo AM: Autophagy and the hallmarks of aging. Ageing Res Rev. 72:1014682021. View Article : Google Scholar : PubMed/NCBI

17 

Lee JH, Yang DS, Goulbourne CN, Im E, Stavrides P, Pensalfini A, Chan H, Bouchet-Marquis C, Bleiwas C, Berg MJ, et al: Faulty autolysosome acidification in Alzheimer's disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques. Nat Neurosci. 25:688–701. 2022. View Article : Google Scholar : PubMed/NCBI

18 

Uddin MS, Stachowiak A, Mamun AA, Tzvetkov NT, Takeda S, Atanasov AG, Bergantin LB, Abdel-Daim MM and Stankiewicz AM: Autophagy and Alzheimer's Disease: From molecular mechanisms to therapeutic implications. Front Aging Neurosci. 10:042018. View Article : Google Scholar : PubMed/NCBI

19 

Nixon RA: The role of autophagy in neurodegenerative disease. Nat Med. 19:983–997. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Palmer JE, Wilson N, Son SM, Obrocki P, Wrobel L, Rob M, Takla M, Korolchuk VI and Rubinsztein DC: Autophagy, aging, and age-related neurodegeneration. Neuron. 113:29–48. 2025. View Article : Google Scholar

21 

Fang EF, Hou Y, Palikaras K, Adriaanse BA, Kerr JS, Yang B, Lautrup S, Hasan-Olive MM, Caponio D, Dan X, et al: Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nat Neurosci. 22:401–412. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Menzies FM, Fleming A, Caricasole A, Bento CF, Andrews SP, Ashkenazi A, Füllgrabe J, Jackson A, Jimenez Sanchez M, Karabiyik C, et al: Autophagy and neurodegeneration: Pathogenic mechanisms and therapeutic opportunities. Neuron. 93:1015–1034. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Sharif K, Watad A, Bragazzi NL, Lichtbroun M, Amital H and Shoenfeld Y: Physical activity and autoimmune diseases: Get moving and manage the disease. Autoimmun Rev. 17:53–72. 2018. View Article : Google Scholar

24 

Zhu C, Ma H, He A, Li Y, He C and Xia Y: Exercise in cancer prevention and anticancer therapy: Efficacy, molecular mechanisms and clinical information. Cancer Lett. 544:2158142022. View Article : Google Scholar : PubMed/NCBI

25 

Andersen LL: Health promotion and chronic disease prevention at the workplace. Annu Rev Public Health. 45:337–357. 2024. View Article : Google Scholar

26 

Halon-Golabek M, Borkowska A, Herman-Antosiewicz A and Antosiewicz J: Iron Metabolism of the skeletal muscle and neurodegeneration. Front Neurosci. 13:1652019. View Article : Google Scholar : PubMed/NCBI

27 

López-Ortiz S, Pinto-Fraga J, Valenzuela PL, Martín-Hernández J, Seisdedos MM, García-López O, Toschi N, Di Giuliano F, Garaci F, Mercuri NB, et al: Physical exercise and Alzheimer's disease: Effects on pathophysiological molecular pathways of the disease. Int J Mol Sci. 22:28972021. View Article : Google Scholar : PubMed/NCBI

28 

Mahalakshmi B, Maurya N, Lee SD and Bharath Kumar V: Possible neuroprotective mechanisms of physical exercise in neurodegeneration. Int J Mol Sci. 21:58952020. View Article : Google Scholar : PubMed/NCBI

29 

Sujkowski A, Hong L, Wessells RJ and Todi SV: The protective role of exercise against age-related neurodegeneration. Ageing Res Rev. 74:1015432022. View Article : Google Scholar

30 

De la Rosa A, Olaso-Gonzalez G, Arc-Chagnaud C, Millan F, Salvador-Pascual A, García-Lucerga C, Blasco-Lafarga C, Garcia-Dominguez E, Carretero A, Correas AG, et al: Physical exercise in the prevention and treatment of Alzheimer's disease. J Sport Health Sci. 9:394–404. 2020. View Article : Google Scholar : PubMed/NCBI

31 

Fox FAU, Diers K, Lee H, Mayr A, Reuter M, Breteler MMB and Aziz NA: Association between accelerometer-derived physical activity measurements and brain structure: A Population-based cohort study. Neurology. 99:e1202–e1215. 2022. View Article : Google Scholar : PubMed/NCBI

32 

Yau WW, Kirn DR, Rabin JS, Properzi MJ, Schultz AP, Shirzadi Z, Palmgren K, Matos P, Maa C, Pruzin JJ, et al: Physical activity as a modifiable risk factor in preclinical Alzheimer's disease. Nat Med. 31:4075–4083. 2025. View Article : Google Scholar : PubMed/NCBI

33 

Cotman CW, Berchtold NC and Christie LA: Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends Neurosci. 30:464–472. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Kang J, Liu M, Yang Q, Dang X, Li Q, Wang T, Qiu B, Zhang Y, Guo X, Li X, et al: Exercise training exerts beneficial effects on Alzheimer's disease through multiple signaling pathways. Front Aging Neurosci. 17:15580782025. View Article : Google Scholar : PubMed/NCBI

35 

Nixon RA and Rubinsztein DC: Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases. Nat Rev Mol Cell Biol. 25:926–946. 2024. View Article : Google Scholar : PubMed/NCBI

36 

Mizushima N and Komatsu M: Autophagy: Renovation of cells and tissues. Cell. 147:728–741. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Kaur J and Debnath J: Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol. 16:461–472. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Nakatogawa H: Mechanisms governing autophagosome biogenesis. Nat Rev Mol Cell Biol. 21:439–458. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Nazio F and Cecconi F: Autophagy up and down by outsmarting the incredible ULK. Autophagy. 13:967–968. 2017. View Article : Google Scholar : PubMed/NCBI

40 

Gui X, Yang H, Li T, Tan X, Shi P, Li M, Du F and Chen ZJ: Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature. 567:262–266. 2019. View Article : Google Scholar : PubMed/NCBI

41 

Li WW, Li J and Bao JK: Microautophagy: Lesser-known self-eating. Cell Mol Life Sci. 69:1125–1136. 2012. View Article : Google Scholar

42 

Bourdenx M, Martín-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S, Tasset I, Diaz A, Storm NJ, Xin Q, Juste YR, et al: Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell. 184:2696–2714.e25. 2021. View Article : Google Scholar : PubMed/NCBI

43 

Kerr JS, Adriaanse BA, Greig NH, Mattson MP, Cader MZ, Bohr VA and Fang EF: Mitophagy and Alzheimer's disease: Cellular and molecular mechanisms. Trends Neurosci. 40:151–166. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Sulkshane P, Ram J, Thakur A, Reis N, Kleifeld O and Glickman MH: Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia. Redox Biol. 45:1020472021. View Article : Google Scholar : PubMed/NCBI

45 

Zhang Z, Yang X, Song YQ and Tu J: Autophagy in Alzheimer's disease pathogenesis: Therapeutic potential and future perspectives. Ageing Res Rev. 72:1014642021. View Article : Google Scholar : PubMed/NCBI

46 

Deng P, Fan T, Gao P, Peng Y, Li M, Li J, Qin M, Hao R, Wang L, Li M, et al: SIRT5-mediated desuccinylation of RAB7A protects against Cadmium-induced Alzheimer's disease-like pathology by restoring autophagic flux. Adv Sci (Weinh). 11:e24020302024. View Article : Google Scholar : PubMed/NCBI

47 

Xie ZS, Zhao JP, Wu LM, Chu S, Cui ZH, Sun YR, Wang H, Ma HF, Ma DR, Wang P, et al: Hederagenin improves Alzheimer's disease through PPARα/TFEB-mediated autophagy. Phytomedicine. 112:1547112023. View Article : Google Scholar

48 

Shafei MA, Harris M and Conway ME: Divergent metabolic regulation of autophagy and mTORC1-early events in Alzheimer's disease? Front Aging Neurosci. 9:1732017. View Article : Google Scholar : PubMed/NCBI

49 

Wang X and Jia J: Magnolol improves Alzheimer's disease-like pathologies and cognitive decline by promoting autophagy through activation of the AMPK/mTOR/ULK1 pathway. Biomed Pharmacother. 161:1144732023. View Article : Google Scholar : PubMed/NCBI

50 

Zhang XW, Zhu XX, Tang DS and Lu JH: Targeting autophagy in Alzheimer's disease: Animal models and mechanisms. Zool Res. 44:1132–1145. 2023. View Article : Google Scholar : PubMed/NCBI

51 

Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H and Hiltunen M: Impaired autophagy and APP processing in Alzheimer's disease: The potential role of Beclin 1 interactome. Prog Neurobiol. 106-107:33–54. 2013. View Article : Google Scholar : PubMed/NCBI

52 

O'Brien CE and Wyss-Coray T: Sorting through the roles of beclin 1 in microglia and neurodegeneration. J Neuroimmune Pharmacol. 9:285–292. 2014. View Article : Google Scholar : PubMed/NCBI

53 

Longobardi A, Catania M, Geviti A, Salvi E, Vecchi ER, Bellini S, Saraceno C, Nicsanu R, Squitti R, Binetti G, et al: Autophagy markers are altered in Alzheimer's disease, dementia with lewy bodies and frontotemporal dementia. Int J Mol Sci. 25:11252024. View Article : Google Scholar : PubMed/NCBI

54 

Peña-Martinez C, Rickman AD and Heckmann BL: Beyond autophagy: LC3-associated phagocytosis and endocytosis. Sci Adv. 8:eabn17022022. View Article : Google Scholar : PubMed/NCBI

55 

Heckmann BL, Teubner BJW, Tummers B, Boada-Romero E, Harris L, Yang M, Guy CS, Zakharenko SS and Green DR: LC3-Associated Endocytosis facilitates β-Amyloid clearance and mitigates neurodegeneration in murine Alzheimer's disease. Cell. 178:536–551.e14. 2019. View Article : Google Scholar

56 

Udayar V, Chen Y, Sidransky E and Jagasia R: Lysosomal dysfunction in neurodegeneration: Emerging concepts and methods. Trends Neurosci. 45:184–199. 2022. View Article : Google Scholar : PubMed/NCBI

57 

Chae CW, Yoon JH, Lim JR, Park JY, Cho JH, Jung YH, Choi GE, Lee HJ and Han HJ: TRIM16-mediated lysophagy suppresses high-glucose-accumulated neuronal Aβ. Autophagy. 19:2752–2768. 2023. View Article : Google Scholar : PubMed/NCBI

58 

Qian XH, Ding GY, Chen SY, Liu XL, Zhang M and Tang HD: Blood cathepsins on the risk of Alzheimer's disease and related pathological biomarkers: Results from observational cohort and mendelian randomization study. J Prev Alzheimers Dis. 11:1834–1842. 2024. View Article : Google Scholar : PubMed/NCBI

59 

Almeida MF, Bahr BA and Kinsey ST: Endosomal-lysosomal dysfunction in metabolic diseases and Alzheimer's disease. Int Rev Neurobiol. 154:303–324. 2020. View Article : Google Scholar : PubMed/NCBI

60 

Mançano ASF, Pina JG, Froes BR and Sciani JM: Autophagy-lysosomal pathway impairment and cathepsin dysregulation in Alzheimer's disease. Front Mol Biosci. 11:14902752024. View Article : Google Scholar : PubMed/NCBI

61 

Cecarini V, Bonfili L, Gogoi O, Lawrence S, Venanzi FM, Azevedo V, Mancha-Agresti P, Drumond MM, Rossi G, Berardi S, et al: Neuroprotective effects of p62(SQSTM1)-engineered lactic acid bacteria in Alzheimer's disease: A pre-clinical study. Aging. 12:15995–16020. 2020. View Article : Google Scholar : PubMed/NCBI

62 

Thal DR, Gawor K and Moonen S: Regulated cell death and its role in Alzheimer's disease and amyotrophic lateral sclerosis. Acta Neuropathol. 147:692024. View Article : Google Scholar : PubMed/NCBI

63 

Zheng X, Lin W, Jiang Y, Lu K, Wei W, Huo Q, Cui S, Yang X, Li M, Xu N, et al: Electroacupuncture ameliorates beta-amyloid pathology and cognitive impairment in Alzheimer disease via a novel mechanism involving activation of TFEB (transcription factor EB). Autophagy. 17:3833–3847. 2021. View Article : Google Scholar : PubMed/NCBI

64 

Settembre C, Fraldi A, Medina DL and Ballabio A: Signals from the lysosome: A control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol. 14:283–296. 2013. View Article : Google Scholar : PubMed/NCBI

65 

Morais GP, de Sousa Neto IV, Marafon BB, Ropelle ER, Cintra DE, Pauli JR and Silva A: The dual and emerging role of physical exercise-induced TFEB activation in the protection against Alzheimer's disease. J Cell Physiol. 238:954–965. 2023. View Article : Google Scholar : PubMed/NCBI

66 

Nnah IC, Wang B, Saqcena C, Weber GF, Bonder EM, Bagley D, De Cegli R, Napolitano G, Medina DL, Ballabio A, et al: TFEB-driven endocytosis coordinates MTORC1 signaling and autophagy. Autophagy. 15:151–164. 2019. View Article : Google Scholar :

67 

Zhang J, Zhang Y, Wang J, Xia Y, Zhang J and Chen L: Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. Signal Transduct Target Ther. 9:2112024. View Article : Google Scholar : PubMed/NCBI

68 

Dewanjee S, Chakraborty P, Bhattacharya H, Chacko L, Singh B, Chaudhary A, Javvaji K, Pradhan SR, Vallamkondu J, Dey A, et al: Altered glucose metabolism in Alzheimer's disease: Role of mitochondrial dysfunction and oxidative stress. Free Radic Biol Med. 193:134–157. 2022. View Article : Google Scholar : PubMed/NCBI

69 

Chen WT, Lu A, Craessaerts K, Pavie B, Sala Frigerio C, Corthout N, Qian X, Laláková J, Kühnemund M, Voytyuk I, et al: Spatial transcriptomics and in situ sequencing to study Alzheimer's disease. Cell. 182:976–991.e19. 2020. View Article : Google Scholar : PubMed/NCBI

70 

Martini-Stoica H, Xu Y, Ballabio A and Zheng H: The Autophagy-lysosomal pathway in neurodegeneration: A TFEB perspective. Trends Neurosci. 39:221–234. 2016. View Article : Google Scholar : PubMed/NCBI

71 

Wu JJ, Yu H, Bi SG, Wang ZX, Gong J, Mao YM, Wang FZ, Zhang YQ, Nie YJ and Chai GS: Aerobic exercise attenuates autophagy-lysosomal flux deficits by ADRB2/β2-adrenergic receptor-mediated V-ATPase assembly factor VMA21 signaling in APP-PSEN1/PS1 mice. Autophagy. 20:1015–1031. 2024. View Article : Google Scholar :

72 

Bi SG, Yu H, Gao TL, Wu JJ, Mao YM, Gong J, Wang FZ, Yang L, Chen J, Lan ZC, et al: Aerobic exercise attenuates Autophagy-lysosomal flux deficits via β2-AR-Mediated ESCRT-III Subunit CHMP4B in mice with human MAPT P301L. Aging Cell. 24:e701842025. View Article : Google Scholar

73 

Kou X, Chen D and Chen N: Physical activity alleviates cognitive dysfunction of Alzheimer's disease through regulating the mTOR signaling pathway. Int J Mol Sci. 20:15912019. View Article : Google Scholar : PubMed/NCBI

74 

Li HY, Rong SS, Hong X, Guo R, Yang FZ, Liang YY, Li A and So KF: Exercise and retinal health. Restor Neurol Neurosci. 37:571–581. 2019.PubMed/NCBI

75 

Ungvari Z, Fazekas-Pongor V, Csiszar A and Kunutsor SK: The multifaceted benefits of walking for healthy aging: From Blue Zones to molecular mechanisms. Geroscience. 45:3211–3239. 2023. View Article : Google Scholar : PubMed/NCBI

76 

Cassilhas RC, Tufik S and de Mello MT: Physical exercise, neuroplasticity, spatial learning and memory. Cell Mol Life Sci. 73:975–983. 2016. View Article : Google Scholar

77 

Rocchi A, Yamamoto S, Ting T, Fan Y, Sadleir K, Wang Y, Zhang W, Huang S, Levine B, Vassar R and He C: A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease. PLoS Genet. 13:e10069622017. View Article : Google Scholar : PubMed/NCBI

78 

Li X, He Q, Zhao N, Chen X, Li T and Cheng B: High intensity interval training ameliorates cognitive impairment in T2DM mice possibly by improving PI3K/Akt/mTOR Signaling-regulated autophagy in the hippocampus. Brain Res. 1773:1477032021. View Article : Google Scholar : PubMed/NCBI

79 

Chen J, Zhu T, Yang X, Yang Z, Shen M, Gu B, Wang D, Zhang Y, Zhang M, Sun S, et al: Treadmill exercise alleviates STING-mediated microglia pyroptosis and polarization via activating mitophagy post-TBI. Free Radic Biol Med. 239:155–176. 2025. View Article : Google Scholar : PubMed/NCBI

80 

Sun L, Wu L, Xu Z, Zeng W and Wang Y: Running exercise alleviates depressive-like behaviors through the activation of PINK1-Parkin mediated mitophagy in mice exposed to chronic social defeat stress. Psychiatry Res. 352:1167142025. View Article : Google Scholar : PubMed/NCBI

81 

Zhang Y, Liao B, Hu S, Pan SY, Wang GP, Wang YL, Qin ZH and Luo L: High intensity interval training induces dysregulation of mitochondrial respiratory complex and mitophagy in the hippocampus of middle-aged mice. Behav Brain Res. 412:1133842021. View Article : Google Scholar : PubMed/NCBI

82 

Tan ZX, Dong F, Wu LY, Feng YS and Zhang F: The beneficial role of exercise on treating Alzheimer's disease by Inhibiting β-amyloid peptide. Mol Neurobiol. 58:5890–5906. 2021. View Article : Google Scholar : PubMed/NCBI

83 

Gratuze M, Julien J, Morin F, Marette A and Planel E: Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet. Prog Neuropsychopharmacol Biol Psychiatry. 79:452–461. 2017. View Article : Google Scholar : PubMed/NCBI

84 

Xu L, Li M, Wei A, Yang M, Li C, Liu R, Zheng Y, Chen Y, Wang Z, Wang K, et al: Treadmill exercise promotes E3 ubiquitin ligase to remove amyloid β and P-tau and improve cognitive ability in APP/PS1 transgenic mice. J Neuroinflammation. 19:2432022. View Article : Google Scholar

85 

Morais GP, de Sousa Neto IV, Veras ASC, Teixeira GR, Paroschi LO, Pinto AP, Dos Santos JR, Alberici LC, Cintra DEC, Pauli JR, et al: Chronic exercise protects against cognitive deficits in an Alzheimer's disease model by enhancing autophagy and reducing mitochondrial abnormalities. Mol Neurobiol. 62:12791–12810. 2025. View Article : Google Scholar : PubMed/NCBI

86 

Ohia-Nwoko O, Montazari S, Lau YS and Eriksen JL: Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice. Mol Neurodegener. 9:542014. View Article : Google Scholar : PubMed/NCBI

87 

Hussain MS, Agrawal N, Ilma B, M MR, Nayak PP, Kaur M, Khachi A, Goyal K, Rekha A, Gupta S, et al: Autophagy and cellular senescence in Alzheimer's disease: Key drivers of neurodegeneration. CNS Neurosci Ther. 31:e705032025. View Article : Google Scholar : PubMed/NCBI

88 

Saxton RA and Sabatini DM: mTOR signaling in growth, metabolism, and disease. Cell. 168:960–976. 2017. View Article : Google Scholar : PubMed/NCBI

89 

Kim J, Kundu M, Viollet B and Guan KL: AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 13:132–141. 2011. View Article : Google Scholar : PubMed/NCBI

90 

Norwitz NG and Querfurth H: mTOR Mysteries: Nuances and questions about the mechanistic target of rapamycin in neurodegeneration. Front Neurosci. 14:7752020. View Article : Google Scholar : PubMed/NCBI

91 

Gourmaud S, Stewart DA, Irwin DJ, Roberts N, Barbour AJ, Eberwine G, O'Brien WT, Vassar R, Talos DM and Jensen FE: The role of mTORC1 activation in seizure-induced exacerbation of Alzheimer's disease. Brain. 145:324–339. 2022. View Article : Google Scholar :

92 

Babygirija R, Sonsalla MM, Mill J, James I, Han JH, Green CL, Calubag MF, Wade G, Tobon A, Michael J, et al: Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer's disease. Nat Commun. 15:52172024. View Article : Google Scholar : PubMed/NCBI

93 

Watson K and Baar K: mTOR and the health benefits of exercise. Semin Cell Dev Biol. 36:130–139. 2014. View Article : Google Scholar : PubMed/NCBI

94 

Kang EB and Cho JY: Effect of treadmill exercise on PI3K/AKT/mTOR, autophagy, and Tau hyperphosphorylation in the cerebral cortex of NSE/htau23 transgenic mice. J Exerc Nutrition Biochem. 19:199–209. 2015. View Article : Google Scholar : PubMed/NCBI

95 

Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, et al: The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy. Autophagy. 18:496–517. 2022. View Article : Google Scholar :

96 

Shen K, Liu X, Chen D, Chang J, Zhang Y and Kou X: Voluntary wheel-running exercise attenuates brain aging of rats through activating miR-130a-mediated autophagy. Brain Res Bull. 172:203–211. 2021. View Article : Google Scholar : PubMed/NCBI

97 

Wątroba M and Szukiewicz D: The role of sirtuins in aging and age-related diseases. Adv Med Sci. 61:52–62. 2016. View Article : Google Scholar

98 

Wang J, Zhou F, Xiong CE, Wang GP, Chen LW, Zhang YT, Qi SG, Wang ZH, Mei C, Xu YJ, et al: Serum sirtuin1: A potential blood biomarker for early diagnosis of Alzheimer's disease. Aging (Albany NY). 15:9464–9478. 2023. View Article : Google Scholar : PubMed/NCBI

99 

Liu L, Dai WZ, Zhu XC and Ma T: A review of autophagy mechanism of statins in the potential therapy of Alzheimer's disease. J Integr Neurosci. 21:462022. View Article : Google Scholar : PubMed/NCBI

100 

Surya K, Manickam N, Jayachandran KS, Kandasamy M and Anusuyadevi M: Resveratrol mediated regulation of hippocampal neuroregenerative plasticity via SIRT1 pathway in synergy with wnt signaling: Neurotherapeutic implications to mitigate memory loss in Alzheimer's disease. J Alzheimers Dis. 94(Suppl): S125–S140. 2023. View Article : Google Scholar :

101 

Mehramiz M, Porter T, O'Brien EK, Rainey-Smith SR and Laws SM: A potential role for Sirtuin-1 in Alzheimer's disease: Reviewing the biological and environmental evidence. J Alzheimers Dis Rep. 7:823–843. 2023. View Article : Google Scholar : PubMed/NCBI

102 

Zhao N, Xia J and Xu B: Physical exercise may exert its therapeutic influence on Alzheimer's disease through the reversal of mitochondrial dysfunction via SIRT1-FOXO1/3-PINK1-Parkin-mediated mitophagy. J Sport Health Sci. 10:1–3. 2021. View Article : Google Scholar :

103 

Koo JH, Kang EB, Oh YS, Yang DS and Cho JY: Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease. Exp Neurol. 288:142–152. 2017. View Article : Google Scholar

104 

Han R, Liu Y, Li S, Li XJ and Yang W: PINK1-PRKN mediated mitophagy: Differences between in vitro and in vivo models. Autophagy. 19:1396–1405. 2023. View Article : Google Scholar :

105 

Pallanck LJ: Culling sick mitochondria from the herd. J Cell Biol. 191:1225–1227. 2010. View Article : Google Scholar : PubMed/NCBI

106 

Zhao N, Zhang X, Li B, Wang J, Zhang C and Xu B: Treadmill exercise improves PINK1/Parkin-Mediated mitophagy activity against Alzheimer's disease pathologies by upregulated SIRT1-FOXO1/3 Axis in APP/PS1 mice. Mol Neurobiol. 60:277–291. 2023. View Article : Google Scholar

107 

Huang J, Wang X, Zhu Y, Li Z, Zhu YT, Wu JC, Qin ZH, Xiang M and Lin F: Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway. CNS Neurosci Ther. 25:796–807. 2019. View Article : Google Scholar : PubMed/NCBI

108 

Tyagi A and Pugazhenthi S: A Promising strategy to treat neurodegenerative diseases by SIRT3 Activation. Int J Mol Sci. 24:16152023. View Article : Google Scholar : PubMed/NCBI

109 

Khoramipour K, Chamari K, Hekmatikar AA, Ziyaiyan A, Taherkhani S, Elguindy NM and Bragazzi NL: Adiponectin: Structure, physiological functions, role in diseases, and effects of nutrition. Nutrients. 13:11802021. View Article : Google Scholar : PubMed/NCBI

110 

Bloemer J, Pinky PD, Govindarajulu M, Hong H, Judd R, Amin RH, Moore T, Dhanasekaran M, Reed MN and Suppiramaniam V: Role of adiponectin in central nervous system disorders. Neural Plast. 2018:45935302018. View Article : Google Scholar : PubMed/NCBI

111 

Rehman IU, Park JS, Choe K, Park HY, Park TJ and Kim MO: Overview of a novel osmotin abolishes abnormal metabolic-associated adiponectin mechanism in Alzheimer's disease: Peripheral and CNS insights. Ageing Res Rev. 100:1024472024. View Article : Google Scholar : PubMed/NCBI

112 

Ali T, Rehman SU, Khan A, Badshah H, Abid NB, Kim MW, Jo MH, Chung SS, Lee HG, Rutten BPF and Kim MO: Adiponectin-mimetic novel nonapeptide rescues aberrant neuronal metabolic-associated memory deficits in Alzheimer's disease. Mol Neurodegener. 16:232021. View Article : Google Scholar : PubMed/NCBI

113 

Liu B, Liu J, Wang JG, Liu CL and Yan HJ: AdipoRon improves cognitive dysfunction of Alzheimer's disease and rescues impaired neural stem cell proliferation through AdipoR1/AMPK pathway. Exp Neurol. 327:1132492020. View Article : Google Scholar : PubMed/NCBI

114 

Sun F, Wang J, Meng L, Zhou Z, Xu Y, Yang M, Li Y, Jiang T, Liu B and Yan H: AdipoRon promotes amyloid-β clearance through enhancing autophagy via nuclear GAPDH-induced sirtuin 1 activation in Alzheimer's disease. Br J Pharmacol. 181:3039–3063. 2024. View Article : Google Scholar : PubMed/NCBI

115 

Jian Y, Yuan S, Yang J, Lei Y, Li X and Liu W: Aerobic exercise alleviates abnormal autophagy in brain cells of APP/PS1 mice by upregulating AdipoR1 levels. Int J Mol Sci. 23:99212022. View Article : Google Scholar : PubMed/NCBI

116 

Lu TX and Rothenberg ME: MicroRNA. J Allergy Clin Immunol. 141:1202–1207. 2018. View Article : Google Scholar

117 

Kou X and Chen N: Resveratrol as a natural autophagy regulator for prevention and treatment of Alzheimer's disease. Nutrients. 9:9272017. View Article : Google Scholar : PubMed/NCBI

118 

Qi W, Ying Y, Wu P, Dong N, Fu W, Liu Q, Ward N, Dong X, Zhao RC and Wang J: Inhibition of miR-4763-3p expression activates the PI3K/mTOR/Bcl2 autophagy signaling pathway to ameliorate cognitive decline. Int J Biol Sci. 20:5999–6017. 2024. View Article : Google Scholar : PubMed/NCBI

119 

Madadi S, Schwarzenbach H, Saidijam M, Mahjub R and Soleimani M: Potential microRNA-related targets in clearance pathways of amyloid-β: Novel therapeutic approach for the treatment of Alzheimer's disease. Cell Biosci. 9:912019. View Article : Google Scholar

120 

Kou X, Chen D and Chen N: The regulation of microRNAs in Alzheimer's sisease. Front Neurol. 11:2882020. View Article : Google Scholar

121 

Zhang H, Liang J and Chen N: The potential role of miRNA-Regulated autophagy in Alzheimer's disease. Int J Mol Sci. 23:77892022. View Article : Google Scholar : PubMed/NCBI

122 

Kou X, Li J, Liu X, Chang J, Zhao Q, Jia S, Fan J and Chen N: Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics. J Appl Physiol (1985). 122:1462–1469. 2017. View Article : Google Scholar : PubMed/NCBI

123 

Chen P, Chen F, Lei J, Li Q and Zhou B: Activation of the miR-34a-Mediated SIRT1/mTOR signaling pathway by urolithin a attenuates D-Galactose-induced brain aging in mice. Neurotherapeutics. 16:1269–1282. 2019. View Article : Google Scholar : PubMed/NCBI

124 

Chen ML, Hong CG, Yue T, Li HM, Duan R, Hu WB, Cao J, Wang ZX, Chen CY, Hu XK, et al: Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer's disease by enhancing autophagy. Theranostics. 11:2395–2409. 2021. View Article : Google Scholar : PubMed/NCBI

125 

Wang Y, Sun X, He B and Yu S: Ginsenoside Rg1 downregulates miR-9-5p expression to modulate SIRT1-Mediated mitochondrial dysfunction and Ameliorate Alzheimer's disease. Mol Neurobiol. 62:13044–13059. 2025. View Article : Google Scholar : PubMed/NCBI

126 

Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, et al: A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 481:463–468. 2012. View Article : Google Scholar

127 

Lourenco MV, Frozza RL, de Freitas GB, Zhang H, Kincheski GC, Ribeiro FC, Gonçalves RA, Clarke JR, Beckman D, Staniszewski A, et al: Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models. Nat Med. 25:165–175. 2019. View Article : Google Scholar : PubMed/NCBI

128 

Zhang H, Wu X, Liang J, Kirberger M and Chen N: Irisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process. Ageing Res Rev. 80:1016802022. View Article : Google Scholar : PubMed/NCBI

129 

de Freitas GB, Lourenco MV and De Felice FG: Protective actions of exercise-related FNDC5/Irisin in memory and Alzheimer's disease. J Neurochem. 155:602–611. 2020. View Article : Google Scholar : PubMed/NCBI

130 

Ratne N, Jari S, Tadas M, Katariya R, Kale M, Kotagale N, Madia D, Umekar M and Taksande B: Neurobiological role and therapeutic potential of exercise-induced irisin in Alzheimer's disease management. Ageing Res Rev. 105:1026872025. View Article : Google Scholar : PubMed/NCBI

131 

Islam MR, Valaris S, Young MF, Haley EB, Luo R, Bond SF, Mazuera S, Kitchen RR, Caldarone BJ, Bettio LEB, et al: Exercise hormone irisin is a critical regulator of cognitive function. Nat Metab. 3:1058–1070. 2021. View Article : Google Scholar : PubMed/NCBI

132 

Lourenco MV: Irisin limits amyloid-β buildup in Alzheimer's disease. Trends Endocrinol Metab. 35:94–96. 2024. View Article : Google Scholar

133 

Kim E, Kim H, Jedrychowski MP, Bakiasi G, Park J, Kruskop J, Choi Y, Kwak SS, Quinti L, Kim DY, et al: Irisin reduces amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling. Neuron. 111:3619–3633.e8. 2023. View Article : Google Scholar

134 

Bellettini-Santos T, Batista-Silva H, Marcolongo-Pereira C, Quintela-Castro FCA, Barcelos RM, Chiepe K, Rossoni JV Jr, Passamani-Ambrosio R, da Silva BS, Chiarelli-Neto O, et al: Move your body toward healthy aging: Potential neuroprotective mechanisms of irisin in Alzheimer's disease. Int J Mol Sci. 24:124402023. View Article : Google Scholar : PubMed/NCBI

135 

Bujak AL, Crane JD, Lally JS, Ford RJ, Kang SJ, Rebalka IA, Green AE, Kemp BE, Hawke TJ, Schertzer JD and Steinberg GR: AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell Metab. 21:883–890. 2015. View Article : Google Scholar : PubMed/NCBI

136 

Sánchez B, Muñoz-Pinto MF and Cano M: Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase. Expert Rev Mol Med. 25:e42022. View Article : Google Scholar : PubMed/NCBI

137 

Rahman MM, Islam MR and Emran TB: Clinically important natural products for Alzheimer's disease. Int J Surg. 104:1068072022. View Article : Google Scholar : PubMed/NCBI

138 

He Z, Zhang H, Li X, Tu S, Wang Z, Han S, Du X, Shen L, Li N and Liu Q: The protective effects of Esculentoside A through AMPK in the triple transgenic mouse model of Alzheimer's disease. Phytomedicine. 109:1545552023. View Article : Google Scholar : PubMed/NCBI

139 

Fan Y, Wang N, Rocchi A, Zhang W, Vassar R, Zhou Y and He C: Identification of natural products with neuronal and metabolic benefits through autophagy induction. Autophagy. 13:41–56. 2017. View Article : Google Scholar :

140 

Thakral S, Yadav A, Singh V, Kumar M, Kumar P, Narang R, Sudhakar K, Verma A, Khalilullah H, Jaremko M and Emwas AH: Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs. Ageing Res Rev. 88:1019602023. View Article : Google Scholar : PubMed/NCBI

141 

Agah S, Akbari A, Sadeghi E, Morvaridzadeh M, Basharat Z, Palmowski A and Heshmati J: Resveratrol supplementation and acute pancreatitis: A comprehensive review. Biomed Pharmacother. 137:1112682021. View Article : Google Scholar : PubMed/NCBI

142 

Li C, Wang N, Zheng G and Yang L: Oral administration of Resveratrol-Selenium-Peptide nanocomposites alleviates Alzheimer's disease-like pathogenesis by inhibiting Aβ aggregation and regulating gut microbiota. ACS Appl Mater Interfaces. 13:46406–46420. 2021. View Article : Google Scholar : PubMed/NCBI

143 

Islam F, Nafady MH, Islam MR, Saha S, Rashid S, Akter A, Or-Rashid MH, Akhtar MF, Perveen A, Md Ashraf G, et al: Resveratrol and neuroprotection: An insight into prospective therapeutic approaches against Alzheimer's disease from bench to bedside. Mol Neurobiol. 59:4384–4404. 2022. View Article : Google Scholar : PubMed/NCBI

144 

Chen JY, Zhu Q, Zhang S, OuYang D and Lu JH: Resveratrol in experimental Alzheimer's disease models: A systematic review of preclinical studies. Pharmacol Res. 150:1044762019. View Article : Google Scholar : PubMed/NCBI

145 

Rahman MH, Akter R, Bhattacharya T, Abdel-Daim MM, Alkahtani S, Arafah MW, Al-Johani NS, Alhoshani NM, Alkeraishan N, Alhenaky A, et al: Resveratrol and neuroprotection: Impact and its therapeutic potential in Alzheimer's disease. Front Pharmacol. 11:6190242020. View Article : Google Scholar

146 

Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, Rissman RA, Raman R and Aisen PS: A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 85:1383–1391. 2015. View Article : Google Scholar : PubMed/NCBI

147 

Broderick TL, Rasool S, Li R, Zhang Y, Anderson M, Al-Nakkash L, Plochocki JH, Geetha T and Babu JR: Neuroprotective effects of chronic resveratrol treatment and exercise training in the 3xTg-AD mouse model of Alzheimer's disease. Int J Mol Sci. 21:73372020. View Article : Google Scholar : PubMed/NCBI

148 

Kou JJ, Shi JZ, He YY, Hao JJ, Zhang HY, Luo DM, Song JK, Yan Y, Xie XM, Du GH and Pang XB: Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation. Acta Pharmacol Sin. 43:840–849. 2022. View Article : Google Scholar

149 

Vongthip W, Nilkhet S, Boonruang K, Sukprasansap M, Tencomnao T and Baek SJ: Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death. Sci Rep. 14:77072024. View Article : Google Scholar : PubMed/NCBI

150 

Ali F and Siddique YH: Bioavailability and Pharmaco-therapeutic potential of luteolin in overcoming Alzheimer's disease. CNS Neurol Disord Drug Targets. 18:352–365. 2019. View Article : Google Scholar : PubMed/NCBI

151 

He Z, Li X, Wang Z, Cao Y, Han S, Li N, Cai J, Cheng S and Liu Q: Protective effects of luteolin against amyloid beta-induced oxidative stress and mitochondrial impairments through peroxisome proliferator-activated receptor γ-dependent mechanism in Alzheimer's disease. Redox Biol. 66:1028482023. View Article : Google Scholar

152 

Tao X, Zhang R, Wang L, Li X and Gong W: Luteolin and exercise combination therapy ameliorates Amyloid-β1-42 Oligomers-Induced cognitive impairment in AD Mice by mediating neuroinflammation and autophagy. J Alzheimers Dis. 92:195–208. 2023. View Article : Google Scholar

153 

Tao X, Wang L and Gong W: Untargeted metabolomics reveals the mechanisms of luteolin and exercise combination treatment against cognitive impairments in AD mice through modulating autophagy. J Nutr Biochem. 145:1100112025. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li W, Wang W, Song Y, Li X, Li Y, Wang X, Tian T, Huang X and Zhao L: Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review). Int J Mol Med 57: 84, 2026.
APA
Li, W., Wang, W., Song, Y., Li, X., Li, Y., Wang, X. ... Zhao, L. (2026). Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review). International Journal of Molecular Medicine, 57, 84. https://doi.org/10.3892/ijmm.2026.5755
MLA
Li, W., Wang, W., Song, Y., Li, X., Li, Y., Wang, X., Tian, T., Huang, X., Zhao, L."Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review)". International Journal of Molecular Medicine 57.4 (2026): 84.
Chicago
Li, W., Wang, W., Song, Y., Li, X., Li, Y., Wang, X., Tian, T., Huang, X., Zhao, L."Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 84. https://doi.org/10.3892/ijmm.2026.5755
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Wang W, Song Y, Li X, Li Y, Wang X, Tian T, Huang X and Zhao L: Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review). Int J Mol Med 57: 84, 2026.
APA
Li, W., Wang, W., Song, Y., Li, X., Li, Y., Wang, X. ... Zhao, L. (2026). Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review). International Journal of Molecular Medicine, 57, 84. https://doi.org/10.3892/ijmm.2026.5755
MLA
Li, W., Wang, W., Song, Y., Li, X., Li, Y., Wang, X., Tian, T., Huang, X., Zhao, L."Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review)". International Journal of Molecular Medicine 57.4 (2026): 84.
Chicago
Li, W., Wang, W., Song, Y., Li, X., Li, Y., Wang, X., Tian, T., Huang, X., Zhao, L."Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 84. https://doi.org/10.3892/ijmm.2026.5755
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team