Modulation of MicroRNAs As a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Jul 18

PMID 32674523

Citations 16

Authors

Alex Cleber Improta-Caria

Carolina Kymie Vasques Nonaka

Bruno Raphael Ribeiro Cavalcante

Ricardo Augusto Leoni De Sousa

Roque Aras Junior

Bruno Solano de Freitas Souza

Affiliations

Soon will be listed here.

Abstract

Alzheimer disease (AD) is one of the most common neurodegenerative diseases, affecting middle-aged and elderly individuals worldwide. AD pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain, along with chronic neuroinflammation and neurodegeneration. Physical exercise (PE) is a beneficial non-pharmacological strategy and has been described as an ally to combat cognitive decline in individuals with AD. However, the molecular mechanisms that govern the beneficial adaptations induced by PE in AD are not fully elucidated. MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of gene expression, inhibiting or degrading their target mRNAs. MicroRNAs are involved in physiological processes that govern normal brain function and deregulated microRNA profiles are associated with the development and progression of AD. It is also known that PE changes microRNA expression profile in the circulation and in target tissues and organs. Thus, this review aimed to identify the role of deregulated microRNAs in the pathophysiology of AD and explore the possible role of the modulation of microRNAs as a molecular mechanism involved in the beneficial actions of PE in AD.

Citing Articles

Identification and Validation of Biomarkers for Alzheimer's Disease Based on Akt and Wnt Signaling Pathways in Mouse Models.

Wang Y, Wu H, Xin C, Zhang K, Zhang J, Zhi H Mol Neurobiol. 2025; .

PMID: 39992588 DOI: 10.1007/s12035-025-04785-w.

LncRNA ILF3-AS1 mediates oxidative stress and inflammation through miR-504-3p/HMGB1 axis in a cellular model of temporal lobe epilepsy.

Gao P, Wu Y, Yan Z Brain Behav. 2024; 14(8):e3615.

PMID: 39135276 PMC: 11319232. DOI: 10.1002/brb3.3615.

Can exercise benefits be harnessed with drugs? A new way to combat neurodegenerative diseases by boosting neurogenesis.

Zhao R Transl Neurodegener. 2024; 13(1):36.

PMID: 39049102 PMC: 11271207. DOI: 10.1186/s40035-024-00428-7.

Efficacy of exercise rehabilitation for managing patients with Alzheimer's disease.

Li D, Jia J, Zeng H, Zhong X, Chen H, Yi C Neural Regen Res. 2024; 19(10):2175-2188.

PMID: 38488551 PMC: 11034587. DOI: 10.4103/1673-5374.391308.

MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype.

Tariq M, Richard V, Kerin M Biomedicines. 2023; 11(11).

PMID: 38002007 PMC: 10669494. DOI: 10.3390/biomedicines11113007.

References

Kou X, Li J, Liu X, Chang J, Zhao Q, Jia S . Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics. J Appl Physiol (1985). 2017; 122(6):1462-1469. DOI: 10.1152/japplphysiol.00018.2017. View

Liu C, Wang J, Li L, Wang P . MicroRNA-384 regulates both amyloid precursor protein and β-secretase expression and is a potential biomarker for Alzheimer's disease. Int J Mol Med. 2014; 34(1):160-6. DOI: 10.3892/ijmm.2014.1780. View

Batkai S, Thum T . MicroRNAs in hypertension: mechanisms and therapeutic targets. Curr Hypertens Rep. 2011; 14(1):79-87. DOI: 10.1007/s11906-011-0235-6. View

Wang X, Liu D, Huang H, Wang Z, Hou T, Yang X . A Novel MicroRNA-124/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer's Disease. Biol Psychiatry. 2017; 83(5):395-405. DOI: 10.1016/j.biopsych.2017.07.023. View

Paolicelli R, Bergamini G, Rajendran L . Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia. Neuroscience. 2018; 405:148-157. DOI: 10.1016/j.neuroscience.2018.04.003. View

Patel N, Hoang D, Miller N, Ansaloni S, Huang Q, Rogers J . MicroRNAs can regulate human APP levels. Mol Neurodegener. 2008; 3:10. PMC: 2529281. DOI: 10.1186/1750-1326-3-10. View

Tanzi R, Haines J, Watkins P, Stewart G, Wallace M, Hallewell R . Genetic linkage map of human chromosome 21. Genomics. 1988; 3(2):129-36. DOI: 10.1016/0888-7543(88)90143-7. View

Lourenco M, Clarke J, Frozza R, Bomfim T, Forny-Germano L, Batista A . TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer's β-amyloid oligomers in mice and monkeys. Cell Metab. 2013; 18(6):831-43. DOI: 10.1016/j.cmet.2013.11.002. View

Abbott M, WELLS D, Fallon J . The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosci. 1999; 19(17):7300-8. PMC: 6782521. View

10.

Lukiw W, Zhao Y, Cui J . An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem. 2008; 283(46):31315-22. PMC: 2581572. DOI: 10.1074/jbc.M805371200. View

11.

Bhattacharjee S, Zhao Y, Dua P, Rogaev E, Lukiw W . microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration. PLoS One. 2016; 11(3):e0150211. PMC: 4780721. DOI: 10.1371/journal.pone.0150211. View

12.

Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R . DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet. 2007; 39(3):380-5. PMC: 3008549. DOI: 10.1038/ng1969. View

13.

Li J, Wang H . miR-15b reduces amyloid-β accumulation in SH-SY5Y cell line through targetting NF-κB signaling and BACE1. Biosci Rep. 2018; 38(6). PMC: 6239251. DOI: 10.1042/BSR20180051. View

14.

Gomes J, Fernandes T, Soci U, Silveira A, Barretti D, Negrao C . Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training. Oxid Med Cell Longev. 2017; 2017:2415246. PMC: 5358469. DOI: 10.1155/2017/2415246. View

15.

Nonaka C, Macedo C, Cavalcante B, Alcantara A, Silva D, da Rocha Bezerra M . Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy. Int J Mol Sci. 2019; 20(16). PMC: 6721092. DOI: 10.3390/ijms20164064. View

16.

Liu X, Xiao J, Zhu H, Wei X, Platt C, Damilano F . miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell Metab. 2015; 21(4):584-95. PMC: 4393846. DOI: 10.1016/j.cmet.2015.02.014. View

17.

Vilardo E, Barbato C, Ciotti M, Cogoni C, Ruberti F . MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons. J Biol Chem. 2010; 285(24):18344-51. PMC: 2881760. DOI: 10.1074/jbc.M110.112664. View

18.

Reaven G . Insulin resistance, type 2 diabetes mellitus, and cardiovascular disease: the end of the beginning. Circulation. 2005; 112(20):3030-2. DOI: 10.1161/CIRCULATIONAHA.105.504670. View

19.

Liu P, Xie Y, Meng X, Kang J . History and progress of hypotheses and clinical trials for Alzheimer's disease. Signal Transduct Target Ther. 2019; 4:29. PMC: 6799833. DOI: 10.1038/s41392-019-0063-8. View

20.

Zhang B, Wang A, Xia C, Lin Q, Chen C . A single nucleotide polymorphism in primary-microRNA-146a reduces the expression of mature microRNA-146a in patients with Alzheimer's disease and is associated with the pathogenesis of Alzheimer's disease. Mol Med Rep. 2015; 12(3):4037-4042. PMC: 4526084. DOI: 10.3892/mmr.2015.3968. View