Epigenetic Mechanisms of Aluminum-Induced Neurotoxicity and Alzheimer's Disease: A Focus on Non-Coding RNAs

被引:1
|
作者
Aschner, Michael [1 ]
Skalny, Anatoly V. [2 ,3 ]
Santamaria, Abel [4 ,5 ]
Rocha, Joao B. T. [6 ]
Mansouri, Borhan [7 ]
Tizabi, Yousef [8 ]
Madeddu, Roberto [9 ]
Lu, Rongzu [10 ]
Lee, Eunsook [11 ]
Tinkov, Alexey A. [2 ,3 ]
机构
[1] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA
[2] Yaroslavl State Univ, Lab Ecobiomonitoring & Qual Control, Sovetskaya Str 14, Yaroslavl 150000, Russia
[3] Sechenov Univ, IM Sechenov Moscow State Med Univ 1, Lab Mol Dietet, Bolshaya Pirogovskaya St 2-4, Moscow 119146, Russia
[4] Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City 04510, Mexico
[5] Univ Autonoma Metropolitana Xochimilco, Dept Atenc Salud, Lab Nanotecnol & Nanomed, Mexico City 04960, Mexico
[6] Univ Fed Santa Maria, Dept Bioquim & Biol Mol, CCNE, Santa Maria, RS, Brazil
[7] Kermanshah Univ Med Sci, Res Inst Hlth, Subst Abuse Prevent Res Ctr, Kermanshah, Iran
[8] Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA
[9] Univ Sassari, Dept Biomed Sci Histol, Viale San Pietro 43-B, I-07100 Sassari, Italy
[10] Jiangsu Univ, Sch Med, Dept Prevent Med & Publ Hlth Lab Sci, Zhenjiang 212013, Jiangsu, Peoples R China
[11] Florida A&M Univ, Dept Pharmaceut Sci, Tallahassee, FL 32307 USA
关键词
Aluminum; microRNA; Long non-coding RNA; DNA methylation; Histone; TAU-PROTEIN PHOSPHORYLATION; DNA METHYLATION; COGNITIVE IMPAIRMENT; DRINKING-WATER; D-GALACTOSE; RAT MODEL; BRAIN; EXPOSURE; RISK; SODIUM;
D O I
10.1007/s11064-024-04214-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aluminum (Al) is known to induce neurotoxic effects, potentially contributing to Alzheimer's disease (AD) pathogenesis. Recent studies suggest that epigenetic modification may contribute to Al neurotoxicity, although the mechanisms are still debatable. Therefore, the objective of the present study was to summarize existing data on the involvement of epigenetic mechanisms in Al-induced neurotoxicity, especially AD-type pathology. Existing data demonstrate that Al exposure induces disruption in DNA methylation, histone modifications, and non-coding RNA expression in brains. Alterations in DNA methylation following Al exposure were shown to be mediated by changes in expression and activity of DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs). Al exposure was shown to reduce histone acetylation by up-regulating expression of histone deacetylases (HDACs) and impair histone methylation, ultimately contributing to down-regulation of brain-derived neurotrophic factor (BDNF) expression and activation of nuclear factor kappa B (NF-kappa B) signaling. Neurotoxic effects of Al exposure were also associated with aberrant expression of non-coding RNAs, especially microRNAs (miR). Al-induced patterns of miR expression were involved in development of AD-type pathology by increasing amyloid beta (A beta) production through up-regulation of A beta precursor protein (APP) and beta secretase (BACE1) expression (down-regulation of miR-29a/b, miR-101, miR-124, and Let-7c expression), increasing in neuroinflammation through NF-kappa B signaling (up-regulation of miR-9, miR-125b, miR-128, and 146a), as well as modulating other signaling pathways. Furthermore, reduced global DNA methylation, altered histone modification, and aberrant miRNA expression were associated with cognitive decline in Al-exposed subjects. However, further studies are required to evaluate the contribution of epigenetic mechanisms to Al-induced neurotoxicity and/or AD development.
引用
收藏
页码:2988 / 3005
页数:18
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