Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review)

Gao,Junyan; Li,Liping

doi:10.3892/etm.2023.12143

Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review)

Authors:
- Junyan Gao
- Liping Li
View Affiliations

Affiliations: Department of Physiology and Pharmacology, Health Science Centre, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
Published online on: August 1, 2023 https://doi.org/10.3892/etm.2023.12143
Article Number: 444
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Alzheimer's disease (AD), the most common cause of dementia worldwide, has gradually become a global health concern for society and individuals with the process of global ageing. Although extensive research has been carried out on AD, the etiology and pathological mechanism of the disease are still unclear, and there is no specific drug to cure or delay AD progression. The exploration of enhancing nerve regeneration in AD has gradually attracted increasing attention. In the current review, the existing therapeutic strategies were summarized to induce nerve regeneration which can increase the number of neurons, and improve the survival of neurons, the plasticity of synapses and synaptic activity. The strategies include increasing neurotrophic expression (such as brain‑derived neurotrophic factor and nerve growth factor), inhibiting acetylcholinesterase (such as donepezil, tacrine, rivastigmine and galanthamine), elevating histone deacetylase levels (such as RGFP‑966, Tasquinimod, CM‑414 and 44B), stimulating the brain by physiotherapy (such as near‑infrared light, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation) and transplanting exogenous neural stem cells. However, further evaluations need to be performed to determine the optimal treatment. The present study reviews recent interventions for enhancing adult neurogenesis and attempts to elucidate their mechanisms of action, which may provide a theoretical basis for inducing nerve regeneration to fight against AD.

View Figures

View References

1	Soria Lopez JA, González HM and Léger GC: Alzheimer's disease. Handb Clin Neurol. 167:231–255. 2019.PubMed/NCBI View Article : Google Scholar
2	Tiwari S, Atluri V, Kaushik A, Yndart A and Nair M: Alzheimer's disease: Pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 14:5541–5554. 2019.PubMed/NCBI View Article : Google Scholar
3	Ayers D and Scerri C: Non-coding RNA influences in dementia. Noncoding RNA Res. 3:188–194. 2018.PubMed/NCBI View Article : Google Scholar
4	Panza F, Lozupone M, Logroscino G and Imbimbo BP: A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol. 15:73–88. 2019.PubMed/NCBI View Article : Google Scholar
5	Gao Y and Tan L, Yu JT and Tan L: Tau in Alzheimer's disease: Mechanisms and therapeutic strategies. Curr Alzheimer Res. 15:283–300. 2018.PubMed/NCBI View Article : Google Scholar
6	Fernández-Calle R, Konings SC, Frontiñán-Rubio J, García-Revilla J, Camprubí-Ferrer L, Svensson M, Martinson I, Boza-Serrano A, Venero JL, Nielsen HM, et al: APOE in the bullseye of neurodegenerative diseases: Impact of the APOE genotype in Alzheimer's disease pathology and brain diseases. Mol Neurodegener. 17(62)2022.PubMed/NCBI View Article : Google Scholar
7	Honjo K, Black SE and Verhoeff NPLG: Alzheimer's disease, cerebrovascular disease, and the β-amyloid cascade. Can J Neurol Sci. 39:712–728. 2012.PubMed/NCBI View Article : Google Scholar
8	Sharma K: Cholinesterase inhibitors as Alzheimer's therapeutics (review). Mol Med Rep. 20:1479–1487. 2019.PubMed/NCBI View Article : Google Scholar
9	Hynd MR, Scott HL and Dodd PR: Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Int. 45:583–595. 2004.PubMed/NCBI View Article : Google Scholar
10	Sun MK: Roles of neural regeneration in memory pharmacology. Neural Regen Res. 13:406–407. 2018.PubMed/NCBI View Article : Google Scholar
11	Altman J and Das GD: Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol. 124:319–335. 1965.PubMed/NCBI View Article : Google Scholar
12	von Bohlen Und Halbach O: Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res. 329:409–420. 2007.PubMed/NCBI View Article : Google Scholar
13	Low VF, Faull RL, Bennet L, Gunn AJ and Curtis MA: Neurogenesis and progenitor cell distribution in the subgranular zone and subventricular zone of the adult sheep brain. Neuroscience. 244:173–187. 2013.PubMed/NCBI View Article : Google Scholar
14	Gould E, Reeves AJ, Graziano MS and Gross CG: Neurogenesis in the neocortex of adult primates. Science. 286:548–552. 1999.PubMed/NCBI View Article : Google Scholar
15	Farzanehfar P: Comparative review of adult midbrain and striatum neurogenesis with classical neurogenesis. Neurosci Res. 134:1–9. 2018.PubMed/NCBI View Article : Google Scholar
16	Tobin MK, Musaraca K, Disouky A, Shetti A, Bheri A, Honer WG, Kim N, Dawe RJ, Bennett DA, Arfanakis K and Lazarov O: Human hippocampal neurogenesis persists in aged adults and Alzheimer's disease patients. Cell Stem Cell. 24:974–982.e3. 2019.PubMed/NCBI View Article : Google Scholar
17	Scheff SW, Price DA, Schmitt FA and Mufson EJ: Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 27:1372–1384. 2006.PubMed/NCBI View Article : Google Scholar
18	Wang YJ, Gong WG, Ren QG and Zhang ZJ: Escitalopram alleviates Alzheimer's disease-type tau pathologies in the aged P301L tau transgenic mice. J Alzheimers Dis. 77:807–819. 2020.PubMed/NCBI View Article : Google Scholar
19	Zhang L, Qin Z, Sharmin F, Lin W, Ricke KM, Zasloff MA, Stewart AFR and Chen HH: Tyrosine phosphatase PTP1B impairs presynaptic NMDA receptor-mediated plasticity in a mouse model of Alzheimer's disease. Neurobiol Dis. 156(105402)2021.PubMed/NCBI View Article : Google Scholar
20	Yang XB, Zu HB, Zhao YF and Yao K: Agomelatine prevents amyloid plaque deposition, tau phosphorylation, and neuroinflammation in APP/PS1 mice. Front Aging Neurosci. 13(766410)2022.PubMed/NCBI View Article : Google Scholar
21	Duan S, Guan X, Lin R, Liu X, Yan Y, Lin R, Zhang T, Chen X, Huang J, Sun X, et al: Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: A dual-target drug for the treatment of Alzheimer's disease. Neurobiol Aging. 36:1792–1807. 2015.PubMed/NCBI View Article : Google Scholar
22	He Z, Li X, Wang Z, Tu S, Feng J, Du X, Ni J, Li N and Liu Q: Esculentoside A alleviates cognitive deficits and amyloid pathology through peroxisome proliferator-activated receptor γ-dependent mechanism in an Alzheimer's disease model. Phytomedicine. 98(153956)2022.PubMed/NCBI View Article : Google Scholar : (Epub ahead of print).
23	Wang C, Zheng D, Weng F, Jin Y and He L: Sodium butyrate ameliorates the cognitive impairment of Alzheimer's disease by regulating the metabolism of astrocytes. Psychopharmacology (Berl). 239:215–227. 2022.PubMed/NCBI View Article : Google Scholar
24	Zhang HA, Yuan CX, Liu KF, Yang QF, Zhao J, Li H, Yang QH, Song D, Quan ZZ and Qing H: Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy. Neural Regen Res. 17:152–162. 2022.PubMed/NCBI View Article : Google Scholar
25	Lilja AM, Malmsten L, Röjdner J, Voytenko L, Verkhratsky A, Ögren SO, Nordberg A and Marutle A: Neural stem cell transplant-induced effect on neurogenesis and cognition in Alzheimer Tg2576 mice is inhibited by concomitant treatment with amyloid-lowering or cholinergic α7 nicotinic receptor drugs. Neural Plast. 2015(370432)2015.PubMed/NCBI View Article : Google Scholar
26	Li W, Kong LH, Wang H, Shen F, Wang YW, Zhou H and Sun GJ: High-frequency electroacupuncture evidently reinforces hippocampal synaptic transmission in Alzheimer's disease rats. Neural Regen Res. 11:801–806. 2016.PubMed/NCBI View Article : Google Scholar
27	Riolo G, Ricci C, De Angelis N, Marzocchi C, Guerrera G, Borsellino G, Giannini F and Battistini S: BDNF and pro-BDNF in amyotrophic lateral sclerosis: A new perspective for biomarkers of neurodegeneration. Brain Sci. 12(617)2022.PubMed/NCBI View Article : Google Scholar
28	Levey AI, Qiu D, Zhao L, Hu WT, Duong DM, Higginbotham L, Dammer EB, Seyfried NT, Wingo TS, Hales CM, et al: A phase II study repurposing atomoxetine for neuroprotection in mild cognitive impairment. Brain. 145:1924–1938. 2022.PubMed/NCBI View Article : Google Scholar
29	Zoladz JA, Majerczak J, Zeligowska E, Mencel J, Jaskolski A, Jaskolska A and Marusiak J: Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson's disease patients. J Physiol Pharmacol. 65:441–448. 2014.PubMed/NCBI
30	Eyileten C, Sharif L, Wicik Z, Jakubik D, Jarosz-Popek J, Soplinska A, Postula M, Czlonkowska A, Kaplon-Cieslicka A and Mirowska-Guzel D: The relation of the brain-derived neurotrophic factor with MicroRNAs in neurodegenerative diseases and ischemic stroke. Mol Neurobiol. 58:329–347. 2021.PubMed/NCBI View Article : Google Scholar
31	Ball S, Marangell LB, Lipsius S and Russell JM: Brain-derived neurotrophic factor in generalized anxiety disorder: results from a duloxetine clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 43:217–221. 2013.PubMed/NCBI View Article : Google Scholar
32	Shekari A and Fahnestock M: Retrograde axonal transport of BDNF and proNGF diminishes with age in basal forebrain cholinergic neurons. Neurobiol Aging. 84:131–140. 2019.PubMed/NCBI View Article : Google Scholar
33	Thoenen H, Zafra F, Hengerer B and Lindholm D: The synthesis of nerve growth factor and brain-derived neurotrophic factor in hippocampal and cortical neurons is regulated by specific transmitter systems. Ann N Y Acad Sci. 640:86–90. 1991.PubMed/NCBI View Article : Google Scholar
34	Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, et al: Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med. 15:331–337. 2009.PubMed/NCBI View Article : Google Scholar
35	Arora S, Kanekiyo T and Singh J: Functionalized nanoparticles for brain targeted BDNF gene therapy to rescue Alzheimer's disease pathology in transgenic mouse model. Int J Biol Macromol. 208:901–911. 2022.PubMed/NCBI View Article : Google Scholar
36	Beeri MS and Sonnen J: Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression. Neurology. 86:702–703. 2016.PubMed/NCBI View Article : Google Scholar
37	Dong BE, Chen H and Sakata K: BDNF deficiency and enriched environment treatment affect neurotransmitter gene expression differently across ages. J Neurochem. 154:41–55. 2020.PubMed/NCBI View Article : Google Scholar
38	Paraskevopoulou F, Herman MA and Rosenmund C: Glutamatergic innervation onto striatal neurons potentiates GABAergic synaptic output. J Neurosci. 39:4448–4460. 2019.PubMed/NCBI View Article : Google Scholar
39	Miyazaki S, Oikawa H, Takekoshi H, Hoshizaki M, Ogata M and Fujikawa T: Anxiolytic effects of acanthopanax senticosus HARMS occur via regulation of autonomic function and activate hippocampal BDNF-TrkB signaling. Molecules. 24(132)2018.PubMed/NCBI View Article : Google Scholar
40	Li Y, Xiang L, Wang C, Song Y, Miao J and Miao M: Protection against acute cerebral ischemia/reperfusion injury by leonuri herba total alkali via modulation of BDNF-TrKB-PI3K/Akt signaling pathway in rats. Biomed Pharmacother. 133(111021)2021.PubMed/NCBI View Article : Google Scholar
41	Yamaguchi A, Tamatani M, Matsuzaki H, Namikawa K, Kiyama H, Vitek MP, Mitsuda N and Tohyama M: Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53. J Biol Chem. 276:5256–5264. 2001.PubMed/NCBI View Article : Google Scholar
42	Chimenti MS, Sunzini F, Fiorucci L, Botti E, Fonti GL, Conigliaro P, Triggianese P, Costa L, Caso F, Giunta A, et al: Potential role of cytochrome c and tryptase in psoriasis and psoriatic arthritis pathogenesis: Focus on resistance to apoptosis and oxidative stress. Front Immunol. 9(2363)2018.PubMed/NCBI View Article : Google Scholar
43	Zhou LJ, Mo YB, Bu X, Wang JJ, Bai J, Zhang JW, Cheng AB, Ma JH, Wang YW and Xie YX: Erinacine facilitates the opening of the mitochondrial permeability transition pore through the inhibition of the PI3K/Akt/GSK-3β signaling pathway in human hepatocellular carcinoma. Cell Physiol Biochem. 50:851–867. 2018.PubMed/NCBI View Article : Google Scholar
44	Jiang T, Wang XQ, Ding C and Du XL: Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling. Korean J Physiol Pharmacol. 21:579–589. 2017.PubMed/NCBI View Article : Google Scholar
45	Merkouris S, Barde YA, Binley KE, Allen ND, Stepanov AV, Wu NC, Grande G, Lin CW, Li M, Nan X, et al: Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library. Proc Natl Acad Sci USA. 115:E7023–E7032. 2018.PubMed/NCBI View Article : Google Scholar
46	Tacke C, DiStefano PS, Lindsay RM, Metzdorf K, Zagrebelsky M and Korte M: Actions of the TrkB agonist antibody ZEB85 in regulating the architecture and synaptic plasticity in hippocampal neurons. Front Mol Neurosci. 15(945348)2022.PubMed/NCBI View Article : Google Scholar
47	Chen C, Wang Z, Zhang Z, Liu X, Kang SS, Zhang Y and Ye K: The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease. Proc Natl Acad Sci USA. 115:578–583. 2018.PubMed/NCBI View Article : Google Scholar
48	Fan CH, Lin CW, Huang HJ, Lee-Chen GJ, Sun YC, Lin W, Chen CM, Chang KH, Su MT and Hsieh-Li HM: LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer's disease. Psychopharmacology (Berl). 237:3173–3190. 2020.PubMed/NCBI View Article : Google Scholar
49	Tuszynski MH, Yang JH, Barba D, U HS, Bakay RA, Pay MM, Masliah E, Conner JM, Kobalka P, Roy S and Nagahara AH: Nerve growth factor gene therapy: Activation of neuronal responses in Alzheimer disease. JAMA Neurol. 72:1139–1147. 2015.PubMed/NCBI View Article : Google Scholar
50	Rocco ML, Soligo M, Manni L and Aloe L: Nerve growth factor: Early studies and recent clinical trials. Curr Neuropharmacol. 16:1455–1465. 2018.PubMed/NCBI View Article : Google Scholar
51	Ding XW, Li R, Geetha T, Tao YX and Babu JR: Nerve growth factor in metabolic complications and Alzheimer's disease: Physiology and therapeutic potential. Biochim Biophys Acta Mol Basis Dis. 1866(165858)2020.PubMed/NCBI View Article : Google Scholar
52	Tiveron C, Fasulo L, Capsoni S, Malerba F, Marinelli S, Paoletti F, Piccinin S, Scardigli R, Amato G, Brandi R, et al: ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death Differ. 20:1017–1030. 2013.PubMed/NCBI View Article : Google Scholar
53	Mitra S, Behbahani H and Eriksdotter M: Innovative therapy for Alzheimer's disease-with focus on biodelivery of NGF. Front Neurosci. 13(38)2019.PubMed/NCBI View Article : Google Scholar
54	Ruberti F, Capsoni S, Comparini A, Di Daniel E, Franzot J, Gonfloni S, Rossi G, Berardi N and Cattaneo A: Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy. J Neurosci. 20:2589–2601. 2000.PubMed/NCBI View Article : Google Scholar
55	Soligo M, Albini M, Bertoli FL, Marzano V, Protto V, Bracci-Laudiero L, Minnone G, De Benedetti F, Chiaretti A, Mantuano E and Manni L: Different responses of PC12 cells to different pro-nerve growth factor protein variants. Neurochem Int. 129(104498)2019.PubMed/NCBI View Article : Google Scholar
56	Isaev NK, Stelmashook EV and Genrikhs EE: Role of nerve growth factor in plasticity of forebrain cholinergic neurons. Biochemistry (Mosc). 82:291–300. 2017.PubMed/NCBI View Article : Google Scholar
57	Delivanoglou N, Boziki M, Theotokis P, Kesidou E, Touloumi O, Dafi N, Nousiopoulou E, Lagoudaki R, Grigoriadis N, Charalampopoulos I and Simeonidou C: Spatio-temporal expression profile of NGF and the two-receptor system, TrkA and p75NTR, in experimental autoimmune encephalomyelitis. J Neuroinflammation. 17(41)2020.PubMed/NCBI View Article : Google Scholar
58	Yan T, Zhang Z and Li D: NGF receptors and PI3K/AKT pathway involved in glucose fluctuation-induced damage to neurons and α-lipoic acid treatment. BMC Neurosci. 21(38)2020.PubMed/NCBI View Article : Google Scholar
59	Ioannou MS and Fahnestock M: ProNGF, but not NGF, switches from neurotrophic to apoptotic activity in response to reductions in TrkA receptor levels. Int J Mol Sci. 18(599)2017.PubMed/NCBI View Article : Google Scholar
60	Karami A, Eyjolfsdottir H, Vijayaraghavan S, Lind G, Almqvist P, Kadir A, Linderoth B, Andreasen N, Blennow K, Wall A, et al: Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease. Alzheimers Dement. 11:1316–1328. 2015.PubMed/NCBI View Article : Google Scholar
61	Pakzaban P and Chiocca EA: Nerve growth factor protects against herpes simplex virus type 1 neurotoxicity in the rat striatum. Neuroreport. 5:993–996. 1994.PubMed/NCBI View Article : Google Scholar
62	De Rosa R, Garcia AA, Braschi C, Capsoni S, Maffei L, Berardi N and Cattaneo A: Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice. Proc Natl Acad Sci USA. 102:3811–3816. 2005.PubMed/NCBI View Article : Google Scholar
63	Lambiase A, Pagani L, Di Fausto V, Sposato V, Coassin M, Bonini S and Aloe L: Nerve growth factor eye drop administrated on the ocular surface of rodents affects the nucleus basalis and septum: Biochemical and structural evidence. Brain Res. 1127:45–51. 2007.PubMed/NCBI View Article : Google Scholar
64	Hohsfield LA, Geley S, Reindl M and Humpel C: The generation of NGF-secreting primary rat monocytes: A comparison of different transfer methods. J Immunol Methods. 391:112–124. 2013.PubMed/NCBI View Article : Google Scholar
65	Eriksdotter M, Navarro-Oviedo M, Mitra S, Wahlberg L, Linderoth B, Tjernberg LO and Behbahani H: Cerebrospinal fluid from Alzheimer patients affects cell-mediated nerve growth factor production and cell survival in vitro. Exp Cell Res. 371:175–184. 2018.PubMed/NCBI View Article : Google Scholar
66	Moyano P, Flores A, Garcia J, García JM, Anadon MJ, Frejo MT, Sola E, Pelayo A and Del Pino J: Bisphenol A single and repeated treatment increases HDAC2, leading to cholinergic neurotransmission dysfunction and SN56 cholinergic apoptotic cell death through AChE variants overexpression and NGF/TrkA/P75^NTR signaling disruption. Food Chem Toxicol. 157(112614)2021.PubMed/NCBI View Article : Google Scholar
67	Eyjolfsdottir H, Eriksdotter M, Linderoth B, Lind G, Juliusson B, Kusk P, Almkvist O, Andreasen N, Blennow K, Ferreira D, et al: Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: Application of a second-generation encapsulated cell biodelivery device. Alzheimers Res Ther. 8(30)2016.PubMed/NCBI View Article : Google Scholar
68	Amaral LD, Santos NAGD, Sisti FM, Del Bel E and Santos ACD: The antibiotic doxycycline mimics the NGF signaling in PC12 cells: A relevant mechanism for neuroprotection. Chem Biol Interact. 341(109454)2021.PubMed/NCBI View Article : Google Scholar
69	James ML, Belichenko NP, Shuhendler AJ, Hoehne A, Andrews LE, Condon C, Nguyen TV, Reiser V, Jones P, Trigg W, et al: [18F]GE-180 PET detects reduced microglia activation after LM11A-31 therapy in a mouse model of Alzheimer's disease. Theranostics. 7:1422–1436. 2017.PubMed/NCBI View Article : Google Scholar
70	Bartus RT, Dean RL III, Beer B and Lippa AS: The cholinergic hypothesis of geriatric memory dysfunction. Science. 217:408–414. 1982.PubMed/NCBI View Article : Google Scholar
71	Moss DE: Improving anti-neurodegenerative benefits of acetylcholinesterase inhibitors in Alzheimer's disease: Are irreversible inhibitors the future? Int J Mol Sci. 21(3438)2020.PubMed/NCBI View Article : Google Scholar
72	Korabecny J, Spilovska K, Mezeiova E, Benek O, Juza R, Kaping D and Soukup O: A systematic review on donepezil-based derivatives as potential cholinesterase inhibitors for Alzheimer's disease. Curr Med Chem. 26:5625–5648. 2019.PubMed/NCBI View Article : Google Scholar
73	Parsons CG, Danysz W, Dekundy A and Pulte I: Memantine and cholinesterase inhibitors: Complementary mechanisms in the treatment of Alzheimer's disease. Neurotox Res. 24:358–369. 2013.PubMed/NCBI View Article : Google Scholar
74	Liang J, Li J, Jia R, Wang Y, Wu R, Zhang H, Hang L and Xu Y: Identification of the optimal cognitive drugs among Alzheimer's disease: A Bayesian meta-analytic review. Clin Interv Aging. 13:2061–2073. 2018.PubMed/NCBI View Article : Google Scholar
75	Aguglia E, Onor ML, Saina M and Maso E: An open-label, comparative study of rivastigmine, donepezil and galantamine in a real-world setting. Curr Med Res Opin. 20:1747–1752. 2004.PubMed/NCBI View Article : Google Scholar
76	Nordberg A, Darreh-Shori T, Peskind E, Soininen H, Mousavi M, Eagle G and Lane R: Different cholinesterase inhibitor effects on CSF cholinesterases in Alzheimer patients. Curr Alzheimer Res. 6:4–14. 2009.PubMed/NCBI View Article : Google Scholar
77	Joshi S and Kapur J: N-methyl-D-aspartic acid receptor activation downregulates expression of δ subunit-containing GABAA receptors in cultured hippocampal neurons. Mol Pharmacol. 84:1–11. 2013.PubMed/NCBI View Article : Google Scholar
78	Shih CC, Chen PY, Chen MF and Lee TJF: Differential blockade by huperzine A and donepezil of sympathetic nicotinic acetylcholine receptor-mediated nitrergic neurogenic dilations in porcine basilar arteries. Eur J Pharmacol. 868(172851)2020.PubMed/NCBI View Article : Google Scholar
79	Ito T, Inden M, Ueda T, Asaka Y, Kurita H and Hozumi I: The neuroprotective effects of activated alpha7 nicotinic acetylcholine receptor against mutant copper-zinc superoxide dismutase 1-mediated toxicity. Sci Rep. 10(22157)2020.PubMed/NCBI View Article : Google Scholar
80	Noh MY, Koh SH, Kim Y, Kim HY, Cho GW and Kim SH: Neuroprotective effects of donepezil through inhibition of GSK-3 activity in amyloid-beta-induced neuronal cell death. J Neurochem. 108:1116–1125. 2009.PubMed/NCBI View Article : Google Scholar
81	Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T and Akaike A: alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem. 276:13541–13546. 2001.PubMed/NCBI View Article : Google Scholar
82	Makitani K, Nakagawa S, Izumi Y, Akaike A and Kume T: Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes. J Pharmacol Sci. 134:37–44. 2017.PubMed/NCBI View Article : Google Scholar
83	Arias E, Gallego-Sandin S, Villarroya M, García AG and López MG: Unequal neuroprotection afforded by the acetylcholinesterase inhibitors galantamine, donepezil, and rivastigmine in SH-SY5Y neuroblastoma cells: Role of nicotinic receptors. J Pharmacol Exp Ther. 315:1346–1353. 2005.PubMed/NCBI View Article : Google Scholar
84	Zhao S, Zhang X and Li H: Beyond histone acetylation-writing and erasing histone acylations. Curr Opin Struct Biol. 53:169–177. 2018.PubMed/NCBI View Article : Google Scholar
85	Ganai SA, Ramadoss M and Mahadevan V: Histone deacetylase (HDAC) inhibitors-emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration. Curr Neuropharmacol. 14:55–71. 2016.PubMed/NCBI View Article : Google Scholar
86	Fuller NO, Pirone A, Lynch BA, Hewitt MC, Quinton MS, McKee TD and Ivarsson M: CoREST complex-selective histone deacetylase inhibitors show prosynaptic effects and an improved safety profile to enable treatment of synaptopathies. ACS Chem Neurosci. 10:1729–1743. 2019.PubMed/NCBI View Article : Google Scholar
87	Xu K, Dai XL, Huang HC and Jiang ZF: Targeting HDACs: A promising therapy for Alzheimer's disease. Oxid Med Cell Longev. 2011(143269)2011.PubMed/NCBI View Article : Google Scholar
88	Kumar V, Kundu S, Singh A and Singh S: Understanding the role of histone deacetylase and their inhibitors in neurodegenerative disorders: Current targets and future perspective. Curr Neuropharmacol. 20:158–178. 2022.PubMed/NCBI View Article : Google Scholar
89	Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, et al: HDAC2 negatively regulates memory formation and synaptic plasticity. Nature. 459:55–60. 2009.PubMed/NCBI View Article : Google Scholar
90	Janczura KJ, Volmar CH, Sartor GC, Rao SJ, Ricciardi NR, Lambert G, Brothers SP and Wahlestedt C: Inhibition of HDAC3 reverses Alzheimer's disease-related pathologies in vitro and in the 3xTg-AD mouse model. Proc Natl Acad Sci USA. 115:E11148–E11157. 2018.PubMed/NCBI View Article : Google Scholar
91	Chen YA, Lu CH, Ke CC, Chiu SJ, Chang CW, Yang BH, Gelovani JG and Liu RS: Evaluation of class IIa histone deacetylases expression and in vivo epigenetic imaging in a transgenic mouse model of Alzheimer's disease. Int J Mol Sci. 22(8633)2021.PubMed/NCBI View Article : Google Scholar
92	Li Y, Sang S, Ren W, Pei Y, Bian Y, Chen Y and Sun H: Inhibition of histone deacetylase 6 (HDAC6) as a therapeutic strategy for Alzheimer's disease: A review (2010-2020). Eur J Med Chem. 226(113874)2021.PubMed/NCBI View Article : Google Scholar
93	Cuadrado-Tejedor M, Garcia-Barroso C, Sánchez-Arias JA, Rabal O, Pérez-González M, Mederos S, Ugarte A, Franco R, Segura V, Perea G, et al: A first-in-class small-molecule that acts as a dual inhibitor of HDAC and PDE5 and that rescues hippocampal synaptic impairment in Alzheimer's disease mice. Neuropsychopharmacology. 42:524–539. 2017.PubMed/NCBI View Article : Google Scholar
94	Rabal O, Sánchez-Arias JA, Cuadrado-Tejedor M, de Miguel I, Pérez-González M, García-Barroso C, Ugarte A, Estella-Hermoso de Mendoza A, Sáez E, Espelosin M, et al: Design, synthesis, biological evaluation and in vivo testing of dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors for the treatment of Alzheimer's disease. Eur J Med Chem. 150:506–524. 2018.PubMed/NCBI View Article : Google Scholar
95	Koch G, Martorana A and Caltagirone C: Transcranial magnetic stimulation: Emerging biomarkers and novel therapeutics in Alzheimer's disease. Neurosci Lett. 719(134355)2020.PubMed/NCBI View Article : Google Scholar
96	Bursali C, Özkan FÜ, Kaysin MY, Dortcan N, Aktas I and Külcü DG: Effectiveness of repetitive transcranial magnetic stimulation in patients with failed back surgery syndrome: A double-blind randomized placebo-controlled study. Pain Physician. 24:E23–E30. 2021.PubMed/NCBI
97	Minzenberg MJ and Leuchter AF: The effect of psychotropic drugs on cortical excitability and plasticity measured with transcranial magnetic stimulation: Implications for psychiatric treatment. J Affect Disord. 253:126–140. 2019.PubMed/NCBI View Article : Google Scholar
98	Zhao J, Li Z, Cong Y, Zhang J, Tan M, Zhang H, Geng N, Li M, Yu W and Shan P: Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer's disease patients. Oncotarget. 8:33864–33871. 2017.PubMed/NCBI View Article : Google Scholar
99	Sabbagh M, Sadowsky C, Tousi B, Agronin ME, Alva G, Armon C, Bernick C, Keegan AP, Karantzoulis S, Baror E, et al: Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease. Alzheimers Dement. 16:641–650. 2020.PubMed/NCBI View Article : Google Scholar
100	Saitoh Y, Hosomi K, Mano T, Takeya Y, Tagami S, Mori N, Matsugi A, Jono Y, Harada H, Yamada T and Miyake A: Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan. Front Aging Neurosci. 14(993306)2022.PubMed/NCBI View Article : Google Scholar
101	Ahmed MA, Darwish ES, Khedr EM, El Serogy YM and Ali AM: Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 259:83–92. 2012.PubMed/NCBI View Article : Google Scholar
102	Trojano L, Conson M, Maffei R and Grossi D: Categorical and coordinate spatial processing in the imagery domain investigated by rTMS. Neuropsychologia. 44:1569–1574. 2006.PubMed/NCBI View Article : Google Scholar
103	Turriziani P, Smirni D, Zappalà G, Mangano GR, Oliveri M and Cipolotti L: Enhancing memory performance with rTMS in healthy subjects and individuals with mild cognitive Impairment: The role of the right dorsolateral prefrontal cortex. Front Hum Neurosci. 6(62)2012.PubMed/NCBI View Article : Google Scholar
104	Sanches C, Levy R, Benisty S, Volpe-Gillot L, Habert MO, Kas A, Ströer S, Pyatigorskaya N, Kaglik A, Bourbon A, et al: Testing the therapeutic effects of transcranial direct current stimulation (tDCS) in semantic dementia: A double blind, sham controlled, randomized clinical trial. Trials. 20(632)2019.PubMed/NCBI View Article : Google Scholar
105	Bunai T, Hirosawa T, Kikuchi M, Fukai M, Yokokura M, Ito S, Takata Y, Terada T and Ouchi Y: tDCS-induced modulation of GABA concentration and dopamine release in the human brain: A combination study of magnetic resonance spectroscopy and positron emission tomography. Brain Stimul. 14:154–160. 2021.PubMed/NCBI View Article : Google Scholar
106	Lefebvre S and Liew SL: Anatomical parameters of tDCS to modulate the motor system after stroke: A review. Front Neurol. 8(29)2017.PubMed/NCBI View Article : Google Scholar
107	Boggio PS, Ferrucci R, Mameli F, Martins D, Martins O, Vergari M, Tadini L, Scarpini E, Fregni F and Priori A: Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. Brain Stimul. 5:223–230. 2012.PubMed/NCBI View Article : Google Scholar
108	Batsikadze G, Moliadze V, Paulus W, Kuo MF and Nitsche MA: Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. J Physiol. 591:1987–2000. 2013.PubMed/NCBI View Article : Google Scholar
109	Woods AJ, Antal A, Bikson M, Boggio PS, Brunoni AR, Celnik P, Cohen LG, Fregni F, Herrmann CS, Kappenman ES, et al: A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol. 127:1031–1048. 2016.PubMed/NCBI View Article : Google Scholar
110	Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, et al: Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 540:230–235. 2016.PubMed/NCBI View Article : Google Scholar
111	Bradford A, Barlow A and Chazot PL: Probing the differential effects of infrared light sources IR1072 and IR880 on human lymphocytes: Evidence of selective cytoprotection by IR1072. J Photochem Photobiol B. 81:9–14. 2005.PubMed/NCBI View Article : Google Scholar
112	Grillo SL, Duggett NA, Ennaceur A and Chazot PL: Non-invasive infra-red therapy (1072 nm) reduces β-amyloid protein levels in the brain of an Alzheimer's disease mouse model, TASTPM. J Photochem Photobiol B. 123:13–22. 2013.PubMed/NCBI View Article : Google Scholar
113	Wang M, Cao J, Amakye WK, Gong C, Li Q and Ren J: Mid infrared light treatment attenuates cognitive decline and alters the gut microbiota community in APP/PS1 mouse model. Biochem Biophys Res Commun. 523:60–65. 2020.PubMed/NCBI View Article : Google Scholar
114	Huang N, Yao D, Jiang W, Wei C, Li M, Li W, Mu H, Gao M, Ma Z, Lyu J and Tong Z: Safety and efficacy of 630-nm red light on cognitive function in older adults with mild to moderate Alzheimer's disease: Protocol for a randomized controlled study. Front Aging Neurosci. 12(143)2020.PubMed/NCBI View Article : Google Scholar
115	Figueiro MG and Leggett S: Intermittent light exposures in humans: A case for dual entrainment in the treatment of Alzheimer's disease. Front Neurol. 12(625698)2021.PubMed/NCBI View Article : Google Scholar
116	Ying Y and Wang JZ: Illuminating neural circuits in Alzheimer's disease. Neurosci Bull. 37:1203–1217. 2021.PubMed/NCBI View Article : Google Scholar
117	Ourednik J, Ourednik V, Lynch WP, Schachner M and Snyder EY: Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat Biotechnol. 20:1103–1110. 2002.PubMed/NCBI View Article : Google Scholar
118	Alessandrini M, Preynat-Seauve O, De Bruin K and Pepper MS: Stem cell therapy for neurological disorders. S Afr Med J. 109:70–77. 2019.PubMed/NCBI View Article : Google Scholar
119	Kang JM, Yeon BK, Cho SJ and Suh YH: Stem cell therapy for Alzheimer's disease: A review of recent clinical trials. J Alzheimers Dis. 54:879–889. 2016.PubMed/NCBI View Article : Google Scholar
120	Zhang B, Yan W, Zhu Y, Yang W, Le W, Chen B, Zhu R and Cheng L: Nanomaterials in neural-stem-cell-mediated regenerative medicine: Imaging and treatment of neurological diseases. Adv Mater. 30(e1705694)2018.PubMed/NCBI View Article : Google Scholar
121	Shu H, Guo Z, Chen X, Qi S, Xiong X, Xia S, Huang Q, Lan L, Gong J, Huang S, Yang B, et al: Intracerebral transplantation of neural stem cells restores manganese-induced cognitive deficits in mice. Aging Dis. 12:371–385. 2021.PubMed/NCBI View Article : Google Scholar
122	Csobonyeiova M, Polak S, Zamborsky R and Danisovic L: Recent progress in the regeneration of spinal cord injuries by induced pluripotent stem cells. Int J Mol Sci. 20(3838)2019.PubMed/NCBI View Article : Google Scholar
123	Banda E and Grabel L: Directed differentiation of human embryonic stem cells into neural progenitors. Methods Mol Biol. 1307:289–298. 2016.PubMed/NCBI View Article : Google Scholar
124	Shahbazi E, Mirakhori F, Ezzatizadeh V and Baharvand H: Reprogramming of somatic cells to induced neural stem cells. Methods. 133:21–28. 2018.PubMed/NCBI View Article : Google Scholar
125	Daadi MM: Generation of neural stem cells from induced pluripotent stem cells. Methods Mol Biol. 1919:1–7. 2019.PubMed/NCBI View Article : Google Scholar
126	Matsui T, Akamatsu W, Nakamura M and Okano H: Regeneration of the damaged central nervous system through reprogramming technology: Basic concepts and potential application for cell replacement therapy. Exp Neurol. 260:12–18. 2014.PubMed/NCBI View Article : Google Scholar
127	Zhang L, Dong ZF and Zhang JY: Immunomodulatory role of mesenchymal stem cells in Alzheimer's disease. Life Sci. 246(117405)2020.PubMed/NCBI View Article : Google Scholar
128	Yip S, Aboody KS, Burns M, Imitola J, Boockvar JA, Allport J, Park KI, Teng YD, Lachyankar M, McIntosh T, et al: Neural stem cell biology may be well suited for improving brain tumor therapies. Cancer J. 9:189–204. 2003.PubMed/NCBI View Article : Google Scholar
129	Park KI: Transplantation of neural stem cells: Cellular & gene therapy for hypoxic-ischemic brain injury. Yonsei Med J. 41:825–835. 2000.PubMed/NCBI View Article : Google Scholar
130	Zhao L, Liu JW, Kan BH, Shi HY, Yang LP and Liu XY: Acupuncture accelerates neural regeneration and synaptophysin production after neural stem cells transplantation in mice. World J Stem Cells. 12:1576–1590. 2020.PubMed/NCBI View Article : Google Scholar
131	De Feo D, Merlini A, Laterza C and Martino G: Neural stem cell transplantation in central nervous system disorders: From cell replacement to neuroprotection. Curr Opin Neurol. 25:322–333. 2012.PubMed/NCBI View Article : Google Scholar
132	Yu JH, Seo JH, Lee JY, Lee MY and Cho SR: Induction of Neurorestoration From Endogenous Stem Cells. Cell Transplant. 25:863–882. 2016.PubMed/NCBI View Article : Google Scholar
133	Wu K, Zhang R, Lu Y, Wen L, Li Y, Duan R, Yao Y and Jia Y: Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF-2. J Cell Physiol. 234:21860–21876. 2019.PubMed/NCBI View Article : Google Scholar
134	Sun B, Taing A, Liu H, Nie G, Wang J, Fang Y, Liu L, Xue Y, Shi J, Liao YP, et al: Nerve growth factor-conjugated mesoporous silica nanoparticles promote neuron-like PC12 cell proliferation and neurite growth. J Nanosci Nanotechnol. 16:2390–2393. 2016.PubMed/NCBI View Article : Google Scholar
135	Mili B, Das K, Kumar A, Saxena AC, Singh P, Ghosh S and Bag S: Preparation of NGF encapsulated chitosan nanoparticles and its evaluation on neuronal differentiation potentiality of canine mesenchymal stem cells. J Mater Sci Mater Med. 29(4)2017.PubMed/NCBI View Article : Google Scholar
136	Mortazavi Y, Sheikhsaran F, Khamisipour GK, Soleimani M, Teimuri A and Shokri S: The evaluation of nerve growth factor over expression on neural lineage specific genes in human mesenchymal stem cells. Cell J. 18:189–196. 2016.PubMed/NCBI View Article : Google Scholar
137	Lee HJ, Lim IJ, Park SW, Kim YB, Ko Y and Kim SU: Human neural stem cells genetically modified to express human nerve growth factor (NGF) gene restore cognition in the mouse with ibotenic acid-induced cognitive dysfunction. Cell Transplant. 21:2487–2496. 2012.PubMed/NCBI View Article : Google Scholar
138	Ma Y, Li C, Huang Y, Wang Y, Xia X and Zheng JC: Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a. Cell Commun Signal. 17(96)2019.PubMed/NCBI View Article : Google Scholar
139	Zhang R, Mao W, Niu L, Bao W, Wang Y, Wang Y, Zhu Y, Yang Z, Chen J, Dong J, et al: NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice. Elife. 12(e84493)2023.PubMed/NCBI View Article : Google Scholar
140	Ma Y, Wang K, Pan J, Fan Z, Tian C, Deng X, Ma K, Xia X, Huang Y and Zheng JC: Induced neural progenitor cells abundantly secrete extracellular vesicles and promote the proliferation of neural progenitors via extracellular signal-regulated kinase pathways. Neurobiol Dis. 124:322–334. 2019.PubMed/NCBI View Article : Google Scholar
141	Zhang J, Li S, Li L, Li M, Guo C, Yao J and Mi S: Exosome and exosomal microRNA: Trafficking, sorting, and function. Genomics Proteomics Bioinformatics. 13:17–24. 2015.PubMed/NCBI View Article : Google Scholar
142	Xin H, Wang F, Li Y, Lu QE, Cheung WL, Zhang Y, Zhang ZG and Chopp M: Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from MicroRNA 133b-overexpressing multipotent mesenchymal stromal cells. Cell Transplant. 26:243–257. 2017.PubMed/NCBI View Article : Google Scholar
143	Gan C and Ouyang F: Exosomes released from bone-marrow stem cells ameliorate hippocampal neuronal injury through transferring miR-455-3p. J Stroke Cerebrovasc Dis. 31(106142)2022.PubMed/NCBI View Article : Google Scholar
144	Li D, Zhang P, Yao X, Li H, Shen H, Li X, Wu J and Lu X: Exosomes derived from miR-133b-modified mesenchymal stem cells promote recovery after spinal cord injury. Front Neurosci. 12(845)2018.PubMed/NCBI View Article : Google Scholar
145	Takata T, Nonaka W, Iwama H, Kobara H, Deguchi K, Masugata H, Touge T, Miyamoto O, Nakamura T, Itano T and Masaki T: Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus. Brain Res. 1732(146710)2020.PubMed/NCBI View Article : Google Scholar
146	Zhu Q, Zhang N, Hu N, Jiang R, Lu H, Xuan A, Long D and Chen Y: Neural stem cell transplantation improves learning and memory by protecting cholinergic neurons and restoring synaptic impairment in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease. Mol Med Rep. 21:1172–1180. 2020.PubMed/NCBI View Article : Google Scholar
147	Kim HJ, Seo SW, Chang JW, Lee JI, Kim CH, Chin J, Choi SJ, Kwon H, Yun HJ, Lee JM, et al: Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: A phase 1 clinical trial. Alzheimers Dement (N Y). 1:95–102. 2015.PubMed/NCBI View Article : Google Scholar
148	Gauthier S, Rosa-Neto P, Morais JA and Webster C: World Alzheimer Report, 2021: Journey through the diagnosis of dementia. Alzheimer's Disease International. 2021.