|
1
|
GBD 2016 Stroke Collaborators. Global,
regional, and national burden of stroke, 1990-2016: A systematic
analysis for the Global Burden of Disease Study 2016. Lancet
Neurol. 18:439–458. 2019.PubMed/NCBI View Article : Google Scholar
|
|
2
|
Saini V, Guada L and Yavagal DR: Global
epidemiology of stroke and access to acute ischemic stroke
interventions. Neurology. 97 (Suppl 2):S6–S16. 2021.PubMed/NCBI View Article : Google Scholar
|
|
3
|
Kalogeris T, Baines CP, Krenz M and
Korthuis RJ: Cell biology of ischemia/reperfusion injury. Int Rev
Cell Mol Biol. 98:229–317. 2012.PubMed/NCBI View Article : Google Scholar
|
|
4
|
Zhang Q, Jia M, Wang Y, Wang Q and Wu J:
Cell death mechanisms in cerebral Ischemia-reperfusion injury.
Neurochem Res. 47:3525–3542. 2022.PubMed/NCBI View Article : Google Scholar
|
|
5
|
Wang N, Wang W, Wang X, Mang G, Chen J,
Yan X, Tong Z, Yang Q, Wang M, Chen L, et al: Histone lactylation
boosts reparative gene activation Post-myocardial infarction. Circ
Res. 131:893–908. 2022.PubMed/NCBI View Article : Google Scholar
|
|
6
|
Lv X, Lv Y and Dai X: Lactate, histone
lactylation and cancer hallmarks. Expert Rev Mol Med.
25(e7)2023.PubMed/NCBI View Article : Google Scholar
|
|
7
|
Li X, Yang Y, Zhang B, Lin X, Fu X, An Y,
Zou Y, Wang JX, Wang Z and Yu T: Lactate metabolism in human health
and disease. Signal Transduct Target Ther. 7(305)2022.PubMed/NCBI View Article : Google Scholar
|
|
8
|
Li Z, Gong T, W Q, Zhang Y, Zheng X, Li Y,
Ren B, Peng X and Zhou X: Lysine lactylation regulates metabolic
pathways and biofilm formation in Streptococcus mutans. Sci Signal.
16(eadg1849)2023.PubMed/NCBI View Article : Google Scholar
|
|
9
|
Wu H, Huang H and Zhao Y: Interplay
between metabolic reprogramming and post-translational
modifications: From glycolysis to lactylation. Front Immunol.
14(1211221)2023.PubMed/NCBI View Article : Google Scholar
|
|
10
|
Sun L, Zhang H and Gao P: Metabolic
reprogramming and epigenetic modifications on the path to cancer.
Protein Cell. 13:877–919. 2022.PubMed/NCBI View Article : Google Scholar
|
|
11
|
Li R, Yang Y, Wang H, Zhang T, Duan F, Wu
K, Yang S, Xu K, Jiang X and Sun X: Lactate and lactylation in the
brain: Current progress and perspectives. Cell Mol Neurobiol.
43:2541–2555. 2023.PubMed/NCBI View Article : Google Scholar
|
|
12
|
Yang C, Pan RY, Guan F and Yuan Z: Lactate
metabolism in neurodegenerative diseases. Neural Regen Res.
19:69–74. 2024.PubMed/NCBI View Article : Google Scholar
|
|
13
|
Liu R, Wu J, Guo H, Yao W, Li S, Lu Y, Jia
Y, Liang X, Tang J and Zhang H: Post-translational modifications of
histones: Mechanisms, biological functions, and therapeutic
targets. MedComm (2020). 4(e292)2023.PubMed/NCBI View
Article : Google Scholar
|
|
14
|
Zhang D, Tang Z, Huang H, Zhou G, Cui C,
Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al: Metabolic
regulation of gene expression by histone lactylation. Nature.
574:575–580. 2019.PubMed/NCBI View Article : Google Scholar
|
|
15
|
Niu Q, Xi Y, Guo Y, Piao ZJ, Zhang CR, Li
TY, Li DJ, Li P, Yin YL, Lim V and Kamal NNSNM: Lactylation and
methylation: Dual epigenetic codes and potential therapeutic
targets in myocardial aging. Ageing Res Rev.
112(102849)2025.PubMed/NCBI View Article : Google Scholar
|
|
16
|
Farhana A and Lappin SL: Biochemistry,
lactate dehydrogenase. StatPearls Publishing, 2023.
|
|
17
|
Zhu R, Ye X, Lu X, Xiao L, Yuan M, Zhao H,
Guo D, Meng Y, Han H, Luo S, et al: ACSS2 acts as a lactyl-CoA
synthetase and couples KAT2A to function as a lactyltransferase for
histone lactylation and tumor immune evasion. Cell Metab.
37:361–376.e7. 2025.PubMed/NCBI View Article : Google Scholar
|
|
18
|
An YJ, Jo S, Kim JM, Kim HS, Kim HY, Jeon
SM, Han D, Yook JI, Kang KW and Park S: Lactate as a major
epigenetic carbon source for histone acetylation via nuclear LDH
metabolism. Exp Mol Med. 55:2238–2247. 2023.PubMed/NCBI View Article : Google Scholar
|
|
19
|
Chen J, Huang Z, Chen Y, Tian H, Chai P,
Shen Y, Yao Y, Xu S, Ge S and Jia R: Lactate and lactylation in
cancer. Sig Transduct Target Ther. 10(38)2025.PubMed/NCBI View Article : Google Scholar
|
|
20
|
Peng X and Du J: Histone and non-histone
lactylation: Molecular mechanisms, biological functions, diseases,
and therapeutic targets. Mo Biomed. 6(38)2025.PubMed/NCBI View Article : Google Scholar
|
|
21
|
Zhang J, Wu D, Zeng F, Gu H, Li C, Cata
JP, Guo K, Miao C and Zhang H: Lactate metabolic reprogramming and
histone lactylation modification in sepsis. Int J Biol Sci.
21:5034–5055. 2025.PubMed/NCBI View Article : Google Scholar
|
|
22
|
Schurr A, Miller JJ, Payne RS and Rigor
BM: An increase in lactate output by brain tissue serves to meet
the energy needs of glutamate-activated neurons. J Neurosci.
19:34–39. 1999.PubMed/NCBI View Article : Google Scholar
|
|
23
|
Ricketts TD, Prieto-Dominguez N, Gowda PS
and Ubil E: Mechanisms of macrophage plasticity in the tumor
environment: Manipulating activation state to improve outcomes.
Front Immunol. 12(642285)2021.PubMed/NCBI View Article : Google Scholar
|
|
24
|
Deng J, Li Y, Yin L, Liu S, Li Y, Liao W,
Mu L, Luo X and Qin J: Histone lactylation enhances GCLC expression
and thus promotes chemoresistance of colorectal cancer stem cells
through inhibiting ferroptosis. Cell Death Dis.
16(193)2025.PubMed/NCBI View Article : Google Scholar
|
|
25
|
Merkuri F, Rothstein M and Simoes-Costa M:
Histone lactylation couples cellular metabolism with developmental
gene regulatory networks. Nat Commun. 15(90)2024.PubMed/NCBI View Article : Google Scholar
|
|
26
|
Jiang X, Gao J, Fei X, Geng Y, Yue X, Shi
Z, Cheng X, Zhao T, Fan M, Wu H, et al: Global profiling of protein
lactylation in microglia in experimental high-altitude cerebral
edema. Cell Commun Signal. 22(374)2024.PubMed/NCBI View Article : Google Scholar
|
|
27
|
Yang J and Yu X, Xiao M, Xu H, Tan Z, Lei
Y, Guo Y, Wang W, Xu J, Shi S and Yu X: Histone lactylation-driven
feedback loop modulates cholesterol-linked immunosuppression in
pancreatic cancer. Gut. 74:1859–1872. 2025.PubMed/NCBI View Article : Google Scholar
|
|
28
|
Ma W, Jia K, Cheng H, Xu H, Li Z, Zhang H,
Xie H, Sun H, Yi L, Chen Z, et al: Orphan nuclear receptor NR4A3
promotes vascular calcification via histone lactylation. Circ Res.
134:1427–1447. 2024.PubMed/NCBI View Article : Google Scholar
|
|
29
|
Li X, Chen M, Chen X, He X, Li X, Wei H,
Tan Y, Min J, Azam T, Xue M, et al: TRAP1 drives smooth muscle cell
senescence and promotes atherosclerosis via HDAC3-primed histone H4
lysine 12 lactylation. Eur Heart J. 45:4219–4235. 2024.PubMed/NCBI View Article : Google Scholar
|
|
30
|
Lian B, Zhang J, Yin X, Wang J, Li L, Ju
Q, Wang Y, Jiang Y, Liu X, Chen Y, et al: IRT1 improves lactate
homeostasis in the brain to alleviate Parkinsonism via
deacetylation and inhibition of PKM2. Cell Rep Med.
5(101684)2024.PubMed/NCBI View Article : Google Scholar
|
|
31
|
Meng F, He J, Zhang X, Lyu W, Wei R, Wang
S, Du Z, Wang H, Bi J, Hua X, et al: Histone lactylation
antagonizes senescence and skeletal muscle aging by modulating
Aging-related pathways. Adv Sci (Weinh).
12(e2412747)2025.PubMed/NCBI View Article : Google Scholar
|
|
32
|
Yang Z, Huang C, Wen X, Liu W, Huang X, Li
Y, Zang J, Weng Z, Lu D, Tsang CK, et al: Circular RNA circ-FoxO3
attenuates blood-brain barrier damage by inducing autophagy during
ischemia/reperfusion. Mol Ther. 30:1275–1287. 2022.PubMed/NCBI View Article : Google Scholar
|
|
33
|
Guo X, Liu R, Jia M, Wang Q and Wu J:
Ischemia reperfusion injury induced blood brain barrier dysfunction
and the involved molecular mechanism. Neurochem Res. 48:2320–2334.
2023.PubMed/NCBI View Article : Google Scholar
|
|
34
|
Wang L, Liu Y, Zhang X, Ye Y, Xiong X,
Zhang S, Gu L, Jian Z and Wang H: Endoplasmic reticulum stress and
the unfolded protein response in cerebral Ischemia/Reperfusion
injury. Front Cell Neurosci. 16(864426)2022.PubMed/NCBI View Article : Google Scholar
|
|
35
|
Jin W, Zhao J, Yang E, Wang Y, Wang Q, Wu
Y, Tong F, Tan Y, Zhou J and Kang C: Neuronal STAT3/HIF-1α/PTRF
axis-mediated bioenergetic disturbance exacerbates cerebral
ischemia-reperfusion injury via PLA2G4A. Theranostics.
12:3196–3216. 2022.PubMed/NCBI View Article : Google Scholar
|
|
36
|
Ni H, Li J, Zheng J and Zhou B: Cardamonin
attenuates cerebral ischemia/reperfusion injury by activating the
HIF-1α/VEGFA pathway. Phytother Res. 36:1736–1747. 2022.PubMed/NCBI View Article : Google Scholar
|
|
37
|
Long Y, Liu S, Wan J, Zhang Y, Li D, Yu S,
Shi A, Li N and He F: Brain targeted borneol-baicalin liposome
improves blood-brain barrier integrity after cerebral
ischemia-reperfusion injury via inhibiting HIF-1α/VEGF/eNOS/NO
signal pathway. Biomed Pharmacother. 160(114240)2023.PubMed/NCBI View Article : Google Scholar
|
|
38
|
Chen X, Zhang Y, Wang H, Liu L, Li W and
Xie P: The regulatory effects of lactic acid on neuropsychiatric
disorders. Discov Ment Health. 2(8)2022.PubMed/NCBI View Article : Google Scholar
|
|
39
|
Vannucci RC and Yager JY: Glucose, lactic
acid, and perinatal hypoxic-ischemic brain damage. Pediatr Neurol.
8:3–12. 1992.PubMed/NCBI View Article : Google Scholar
|
|
40
|
Mellström B, Naranjo JR, Foulkes NS,
Lafarga M and Sassone-Corsi P: Transcriptional response to cAMP in
brain: Specific distribution and induction of CREM antagonists.
Neuron. 10:655–665. 1993.PubMed/NCBI View Article : Google Scholar
|
|
41
|
Wu X, Jin W, Liu X, Fu H, Gong P, Xu J,
Cui G, Ni Y, Ke K, Gao Z and Gao Y: Cyclic AMP response element
modulator-1 (CREM-1) involves in neuronal apoptosis after traumatic
brain injury. J Mol Neurosci. 47:357–367. 2012.PubMed/NCBI View Article : Google Scholar
|
|
42
|
Yao Y, Bade R, Li G, Zhang A, Zhao H, Fan
L, Zhu R and Yuan J: Global-scale profiling of differential
expressed Lysine-lactylated proteins in the cerebral endothelium of
cerebral Ischemia-reperfusion injury rats. Cell Mol Neurobiol.
43:1989–2004. 2023.PubMed/NCBI View Article : Google Scholar
|
|
43
|
Xiong XY, Pan XR, Luo XX, Wang YF, Zhang
XX, Yang SH, Zhong ZQ, Liu C, Chen Q, Wang PF, et al:
Astrocyte-derived lactate aggravates brain injury of ischemic
stroke in mice by promoting the formation of protein lactylation.
Theranostics. 14:4297–4317. 2024.PubMed/NCBI View Article : Google Scholar
|
|
44
|
Zhang J, Pan W, Zhang Y, Tan M, Yin Y, Li
Y, Zhang L, Han L, Bai J, Jiang T and Li H: Comprehensive overview
of Nrf2-related epigenetic regulations involved in
ischemia-reperfusion injury. Theranostics. 12:6626–6645.
2022.PubMed/NCBI View Article : Google Scholar
|
|
45
|
Wang L, Zhang X, Xiong X, Zhu H, Chen R,
Zhang S, Chen G and Jian Z: Nrf2 Regulates oxidative stress and its
role in cerebral ischemic stroke. Antioxidants (Basel).
11(2377)2022.PubMed/NCBI View Article : Google Scholar
|
|
46
|
Kapanova G, Tashenova G, Akhenbekova A and
Yılmaz S: Cerebral ischemia reperfusion injury: From public health
perspectives to mechanisms. Folia Neuropathol. 60:384–389.
2022.PubMed/NCBI View Article : Google Scholar
|
|
47
|
Xu X, Gao W, Li L, Hao J, Yang B, Wang T,
Li L, Bai X, Li F, Ren H, et al: Annexin A1 protects against
cerebral ischemia-reperfusion injury by modulating
microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR
pathway. J Neuroinflammation. 18(119)2021.PubMed/NCBI View Article : Google Scholar
|
|
48
|
Cui P, Lu W, Wang J, Wang F, Zhang X, Hou
X, Xu F, Liang Y, Chai G and Hao J: Microglia/macrophages require
vitamin D signaling to restrain neuroinflammation and brain injury
in a murine ischemic stroke model. J Neuroinflammation.
20(63)2023.PubMed/NCBI View Article : Google Scholar
|
|
49
|
Zhong Y, Gu L, Ye Y, Zhu H, Pu B, Wang J,
Li Y, Qiu S, Xiong X and Jian Z: JAK2/STAT3 axis intermediates
Microglia/macrophage polarization during cerebral
ischemia/reperfusion injury. Neuroscience. 496:119–128.
2022.PubMed/NCBI View Article : Google Scholar
|
|
50
|
Josifovska S, Panov S, Hadzi-Petrushev N,
Mitrokhin V, Kamkin A, Stojchevski R, Avtanski D and Mladenov M:
Positive Tetrahydrocurcumin-associated Brain-related metabolomic
implications. Molecules. 28(3734)2023.PubMed/NCBI View Article : Google Scholar
|
|
51
|
Orellana-Urzúa S, Rojas I, Líbano L and
Rodrigo R: Pathophysiology of ischemic stroke: Role of oxidative
stress. Curr Pharm Des. 26:4246–4260. 2020.PubMed/NCBI View Article : Google Scholar
|
|
52
|
Fan YY, Hu WW, Nan F and Chen Z:
Postconditioning-induced neuroprotection, mechanisms and
applications in cerebral ischemia. Neurochem Int. 107:43–56.
2017.PubMed/NCBI View Article : Google Scholar
|
|
53
|
Przykaza Ł: Understanding the connection
between common stroke comorbidities, their associated inflammation,
and the course of the cerebral Ischemia/Reperfusion cascade. Front
Immunol. 12(782569)2021.PubMed/NCBI View Article : Google Scholar
|
|
54
|
Li L, Jiang W, Yu B, Liang H, Mao S, Hu X,
Feng Y, Xu J and Chu L: Quercetin improves cerebral
ischemia/reperfusion injury by promoting microglia/macrophages M2
polarization via regulating PI3K/Akt/NF-κB signaling pathway.
Biomed Pharmacother. 168(115653)2023.PubMed/NCBI View Article : Google Scholar
|
|
55
|
Surinkaew P, Apaijai N, Sawaddiruk P,
Jaiwongkam T, Kerdphoo S, Chattipakorn N and Chattipakorn SC:
Mitochondrial fusion promoter alleviates brain damage in rats with
cardiac Ischemia/Reperfusion injury. J Alzheimers Dis. 77:993–1003.
2020.PubMed/NCBI View Article : Google Scholar
|
|
56
|
Gu Y, Zhou C, Piao Z, Yuan H, Jiang H, Wei
H, Zhou Y, Nan G and Ji X: Cerebral edema after ischemic stroke:
Pathophysiology and underlying mechanisms. Front Neurosci.
16(988283)2022.PubMed/NCBI View Article : Google Scholar
|
|
57
|
Boveris DL and Boveris A: Oxygen delivery
to the tissues and mitochondrial respiration. Front Biosci.
12:1014–1023. 2007.PubMed/NCBI View
Article : Google Scholar
|
|
58
|
Warburg O, Wind F and Negelein E: The
metabolism of tumors in the body. J Gen Physiol. 8:519–530.
1927.PubMed/NCBI View Article : Google Scholar
|
|
59
|
Hohnholt MC, Andersen VH, Bak LK and
Waagepetersen HS: Glucose, lactate and glutamine but not glutamate
support Depolarization-Induced increased respiration in isolated
nerve terminals. Neurochem Res. 42:191–201. 2017.PubMed/NCBI View Article : Google Scholar
|
|
60
|
Sharma NK and Pal JK: Metabolic ink
lactate modulates epigenomic landscape: A concerted role of
Pro-tumor microenvironment and macroenvironment during
carcinogenesis. Curr Mol Med. 21:177–181. 2021.PubMed/NCBI View Article : Google Scholar
|
|
61
|
Faubert B, Li KY, Cai L, Hensley CT, Kim
J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, et al:
Lactate metabolism in human lung tumors. Cell. 171:358–371.e9.
2017.PubMed/NCBI View Article : Google Scholar
|
|
62
|
Gibbs ME and Hertz L: Inhibition of
astrocytic energy metabolism by D-lactate exposure impairs memory.
Neurochem Int. 52:1012–1018. 2008.PubMed/NCBI View Article : Google Scholar
|
|
63
|
Newman LA, Korol DL and Gold PE: Lactate
produced by glycogenolysis in astrocytes regulates memory
processing. PLoS One. 6(e28427)2011.PubMed/NCBI View Article : Google Scholar
|
|
64
|
Steinman MQ, Gao V and Alberini CM: The
role of Lactate-mediated metabolic coupling between astrocytes and
neurons in Long-term memory formation. Front Integr Neurosci.
10(10)2016.PubMed/NCBI View Article : Google Scholar
|
|
65
|
Sun S, Li H, Chen J and Qian Q: Lactic
acid: No longer an inert and End-product of glycolysis. Physiology
(Bethesda). 32:453–463. 2017.PubMed/NCBI View Article : Google Scholar
|
|
66
|
Pellerin L and Magistretti PJ: Glutamate
uptake into astrocytes stimulates aerobic glycolysis: A mechanism
coupling neuronal activity to glucose utilization. Proc Natl Acad
Sci USA. 91:10625–10629. 1994.PubMed/NCBI View Article : Google Scholar
|
|
67
|
Aveseh M, Nikooie R, Sheibani V and
Esmaeili-Mahani S: Endurance training increases brain lactate
uptake during hypoglycemia by up regulation of brain lactate
transporters. Mol Cell Endocrinol. 394:29–36. 2014.PubMed/NCBI View Article : Google Scholar
|
|
68
|
Hu J, Cai M, Shang Q, Li Z, Feng Y, Liu B,
Xue X and Lou S: Elevated lactate by High-intensity interval
training regulates the hippocampal BDNF expression and the
mitochondrial quality control system. Front Physiol.
12(629914)2021.PubMed/NCBI View Article : Google Scholar
|
|
69
|
Hur JY, Frost GR, Wu X, Crump C, Pan SJ,
Wong E, Barros M, Li T, Nie P, Zhai Y, et al: The innate immunity
protein IFITM3 modulates γ-secretase in Alzheimer's disease.
Nature. 586:735–740. 2020.PubMed/NCBI View Article : Google Scholar
|
|
70
|
Inabe K and Kurosaki T: Tyrosine
phosphorylation of B-cell adaptor for phosphoinositide 3-kinase is
required for Akt activation in response to CD19 engagement. Blood.
99:584–589. 2002.PubMed/NCBI View Article : Google Scholar
|
|
71
|
Lambertus M, Øverberg LT, Andersson KA,
Hjelden MS, Hadzic A, Haugen ØP, Storm-Mathisen J, Bergersen LH,
Geiseler S and Morland C: L-lactate induces neurogenesis in the
mouse ventricular-subventricular zone via the lactate receptor
HCA1. Acta Physiol (Oxf). 231(e13587)2021.PubMed/NCBI View Article : Google Scholar
|
|
72
|
Laroche S, Stil A, Germain P, Cherif H,
Chemtob S and Bouchard JF: Participation of L-Lactate and its
receptor HCAR1/GPR81 in neurovisual development. Cells.
10(1640)2021.PubMed/NCBI View Article : Google Scholar
|
|
73
|
Lauritzen KH, Morland C, Puchades M,
Holm-Hansen S, Hagelin EM, Lauritzen F, Attramadal H,
Storm-Mathisen J, Gjedde A and Bergersen LH: Lactate receptor sites
link neurotransmission, neurovascular coupling, and brain energy
metabolism. Cereb Cortex. 24:2784–2795. 2014.PubMed/NCBI View Article : Google Scholar
|
|
74
|
Zhao L, Dong M, Ren M, Li C, Zheng H and
Gao H: Metabolomic analysis identifies lactate as an important
pathogenic factor in Diabetes-associated cognitive decline rats.
Mol Cell Proteomics. 17:2335–2346. 2018.PubMed/NCBI View Article : Google Scholar
|
|
75
|
Yang H, Sun Y, Li Q, Jin F and Dai Y:
Diverse epigenetic regulations of macrophages in atherosclerosis.
Front Cardiovasc Med. 9(868788)2022.PubMed/NCBI View Article : Google Scholar
|
|
76
|
Cai M, Wang H, Song H, Yang R, Wang L, Xue
X, Sun W and Hu J: Lactate is answerable for brain function and
treating brain diseases: Energy substrates and signal molecule.
Front Nutr. 9(800901)2022.PubMed/NCBI View Article : Google Scholar
|
|
77
|
de Bari L, Atlante A, Armeni T and Kalapos
MP: Synthesis and metabolism of methylglyoxal,
S-D-lactoylglutathione and D-lactate in cancer and Alzheimer's
disease. Exploring the crossroad of eternal youth and premature
aging. Ageing Res Rev. 53(100915)2019.PubMed/NCBI View Article : Google Scholar
|
|
78
|
Brooks GA: Lactate as a fulcrum of
metabolism. Redox Biol. 35(101454)2020.PubMed/NCBI View Article : Google Scholar
|
|
79
|
Bergersen LH: Lactate transport and
signaling in the brain: Potential therapeutic targets and roles in
body-brain interaction. J Cereb Blood Flow Metab. 35:176–185.
2015.PubMed/NCBI View Article : Google Scholar
|
|
80
|
Bergersen LH and Gjedde A: Is Lactate a
volume transmitter of metabolic states of the brain? Front
Neuroenergetics. 4(5)2012.PubMed/NCBI View Article : Google Scholar
|
|
81
|
Mächler P, Wyss MT, Elsayed M, Stobart J,
Gutierrez R, von Faber-Castell A, Kaelin V, Zuend M, San Martín A,
Romero-Gómez I, et al: In vivo evidence for a lactate gradient from
astrocytes to neurons. Cell Metab. 23:94–102. 2016.PubMed/NCBI View Article : Google Scholar
|
|
82
|
Philips T, Mironova YA, Jouroukhin Y, Chew
J, Vidensky S, Farah MH, Pletnikov MV, Bergles DE, Morrison BM and
Rothstein JD: MCT1 deletion in oligodendrocyte lineage cells causes
Late-onset hypomyelination and axonal degeneration. Cell Rep.
34(108610)2021.PubMed/NCBI View Article : Google Scholar
|
|
83
|
Debernardi R, Pierre K, Lengacher S,
Magistretti PJ and Pellerin L: Cell-specific expression pattern of
monocarboxylate transporters in astrocytes and neurons observed in
different mouse brain cortical cell cultures. J Neurosci Res.
73:141–155. 2003.PubMed/NCBI View Article : Google Scholar
|
|
84
|
Suzuki A, Stern SA, Bozdagi O, Huntley GW,
Walker RH, Magistretti PJ and Alberini CM: Astrocyte-neuron lactate
transport is required for long-term memory formation. Cell.
144:810–823. 2011.PubMed/NCBI View Article : Google Scholar
|
|
85
|
Ardanaz CG, Ramírez MJ and Solas M: Brain
metabolic alterations in Alzheimer's disease. Int J Mol Sci.
23(3785)2022.PubMed/NCBI View Article : Google Scholar
|
|
86
|
Elizondo-Vega R, Oyarce K, Salgado M,
Barahona MJ, Recabal A, Ordenes P, López S, Pincheira R,
Luz-Crawford P and García-Robles MA: Inhibition of hypothalamic
MCT4 and MCT1-MCT4 expressions affects food intake and alters
orexigenic and anorexigenic neuropeptide expressions. Mol
Neurobiol. 57:896–909. 2020.PubMed/NCBI View Article : Google Scholar
|
|
87
|
Brown TP and Ganapathy V: Lactate/GPR81
signaling and proton motive force in cancer: Role in angiogenesis,
immune escape, nutrition, and Warburg phenomenon. Pharmacol Ther.
206(107451)2020.PubMed/NCBI View Article : Google Scholar
|
|
88
|
Madaan A, Chaudhari P, Nadeau-Vallée M,
Hamel D, Zhu T, Mitchell G, Samuels M, Pundir S, Dabouz R, Howe
Cheng CW, et al: Müller cell-localized G-protein-coupled receptor
81 (Hydroxycarboxylic acid receptor 1) regulates inner retinal
vasculature via Norrin/Wnt pathways. Am J Pathol. 189:1878–1896.
2019.PubMed/NCBI View Article : Google Scholar
|
|
89
|
Yang K, Xu J, Fan M, Tu F, Wang X, Ha T,
Williams DL and Li C: Lactate suppresses macrophage
Pro-inflammatory response to LPS stimulation by inhibition of YAP
and NF-κB activation via GPR81-Mediated signaling. Front Immunol.
11(587913)2020.PubMed/NCBI View Article : Google Scholar
|
|
90
|
Khatib-Massalha E, Bhattacharya S,
Massalha H, Biram A, Golan K, Kollet O, Kumari A, Avemaria F,
Petrovich-Kopitman E, Gur-Cohen S, et al: Lactate released by
inflammatory bone marrow neutrophils induces their mobilization via
endothelial GPR81 signaling. Nat Commun. 11(3547)2020.PubMed/NCBI View Article : Google Scholar
|
|
91
|
Chaudhari P, Madaan A, Rivera JC, Charfi
I, Habelrih T, Hou X, Nezhady M, Lodygensky G, Pineyro G, Muanza T
and Chemtob S: Neuronal GPR81 regulates developmental brain
angiogenesis and promotes brain recovery after a hypoxic ischemic
insult. J Cereb Blood Flow Metab. 42:1294–1308. 2022.PubMed/NCBI View Article : Google Scholar
|
|
92
|
Zhai X, Li J, Li L, Sun Y, Zhang X, Xue Y,
Lv J, Gao Y, Li S, Yan W, et al: L-lactate preconditioning promotes
plasticity-related proteins expression and reduces neurological
deficits by potentiating GPR81 signaling in rat traumatic brain
injury model. Brain Res. 1746(146945)2020.PubMed/NCBI View Article : Google Scholar
|
|
93
|
Morland C, Lauritzen KH, Puchades M,
Holm-Hansen S, Andersson K, Gjedde A, Attramadal H, Storm-Mathisen
J and Bergersen LH: The lactate receptor, G-protein-coupled
receptor 81/hydroxycarboxylic acid receptor 1: Expression and
action in brain. J Neurosci Res. 93:1045–1055. 2015.PubMed/NCBI View Article : Google Scholar
|
|
94
|
Cai W, Dai X, Chen J, Zhao J, Xu M, Zhang
L, Yang B, Zhang W, Rocha M, Nakao T, et al: STAT6/Arg1 promotes
microglia/macrophage efferocytosis and inflammation resolution in
stroke mice. JCI Insight. 4(e131355)2019.PubMed/NCBI View Article : Google Scholar
|
|
95
|
Miyazawa K: A negative regulator or just
an unconcerned passerby: Phosphoinositide 3-kinase signalling in
IL-12 production. J Biochem. 152:497–499. 2012.PubMed/NCBI View Article : Google Scholar
|
|
96
|
Fernandez IE and Eickelberg O: New
cellular and molecular mechanisms of lung injury and fibrosis in
idiopathic pulmonary fibrosis. Lancet. 380:680–688. 2012.PubMed/NCBI View Article : Google Scholar
|
|
97
|
Sica A and Mantovani A: Macrophage
plasticity and polarization: In vivo veritas. J Clin Invest.
122:787–795. 2012.PubMed/NCBI View Article : Google Scholar
|
|
98
|
Hagihara H, Shoji H, Otabi H, Toyoda A,
Katoh K, Namihira M and Miyakawa T: Protein lactylation induced by
neural excitation. Cell Rep. 37(109820)2021.PubMed/NCBI View Article : Google Scholar
|
|
99
|
Jurcau A and Simion A: Neuroinflammation
in cerebral ischemia and Ischemia/Reperfusion injuries: From
pathophysiology to therapeutic strategies. Int J Mol Sci.
23(14)2021.PubMed/NCBI View Article : Google Scholar
|
|
100
|
Halabi S, Sekine E, Verstak B, Gay NJ and
Moncrieffe MC: Structure of the Toll/Interleukin-1 receptor (TIR)
domain of the B-cell adaptor that links phosphoinositide metabolism
with the negative regulation of the Toll-like receptor (TLR)
signalosome. J Biol Chem. 292:652–660. 2017.PubMed/NCBI View Article : Google Scholar
|
|
101
|
Irizarry-Caro RA, Mcdaniel MM, Overcast
GR, Jain VG, Troutman TD and Pasare C: TLR signaling adapter BCAP
regulates inflammatory to reparatory macrophage transition by
promoting histone lactylation. Proc Natl Acad Sci USA.
117:30628–30638. 2020.PubMed/NCBI View Article : Google Scholar
|
|
102
|
Ji X, Lu J, Wang K, Guo Y, Zhao D and Liu
M: Lactylation in ischemic brain injury-metabolic mechanisms,
neuroinflammation, and therapeutic targets: A review. Biomol
Biomed. 26:525–536. 2025.PubMed/NCBI View Article : Google Scholar
|
|
103
|
Moreno-Yruela C, Zhang D, Wei W, Bæk M,
Liu W, Gao J, Danková D, Nielsen AL, Bolding JE, Yang L, et al:
Class I histone deacetylases (HDAC1-3) are histone lysine
delactylases. Sci Adv. 8(eabi6696)2022.PubMed/NCBI View Article : Google Scholar
|
|
104
|
Choi EJ, Jang YY, Choi EJ and Oh CJ: The
role of lactate in immune regulation: A metabolic rheostat via
transporters, receptors, and epigenetic modifiers. Cells.
14(1096)2025.PubMed/NCBI View Article : Google Scholar
|
|
105
|
Morland C, Andersson KA, Haugen ØP, Hadzic
A, Kleppa L, Gille A, Rinholm JE, Palibrk V, Diget EH, Kennedy LH,
et al: Exercise induces cerebral VEGF and angiogenesis via the
lactate receptor HCAR1. Nat Commun. 8(15557)2017.PubMed/NCBI View Article : Google Scholar
|
|
106
|
Chen P, Zuo H, Xiong H, Kolar MJ, Chu Q,
Saghatelian A, Siegwart DJ and Wan Y: Gpr132 sensing of lactate
mediates tumor-macrophage interplay to promote breast cancer
metastasis. Proc Natl Acad Sci USA. 114:580–585. 2017.PubMed/NCBI View Article : Google Scholar
|
|
107
|
Halford S, Veal GJ, Wedge SR, Payne GS,
Bacon CM, Sloan P, Dragoni I, Heinzmann K, Potter S, Salisbury BM,
et al: A phase I dose-escalation study of AZD3965, an oral
monocarboxylate transporter 1 inhibitor, in patients with advanced
cancer. Clin Cancer Res. 29:1429–1439. 2023.PubMed/NCBI View Article : Google Scholar
|
|
108
|
Kumar A, Nader MA and Deep G: Emergence of
extracellular vesicles as ‘liquid biopsy’ for neurological
disorders: Boom or bust. Pharmacol Rev. 76:199–227. 2024.PubMed/NCBI View Article : Google Scholar
|