Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?

被引:17
作者
Brackhan, Mirjam [1 ,2 ]
Arribas-Blazquez, Marina [3 ,4 ]
Lastres-Becker, Isabel [2 ,5 ,6 ,7 ]
机构
[1] Inst Invest Sanitaria La Paz IdiPaz, Madrid 28029, Spain
[2] Inst Invest Biomed Alberto Sols CSIC UAM, C Arturo Duperier 4, Madrid 28029, Spain
[3] Univ Complutense Madrid, Fac Vet Med, Dept Pharmacol & Toxicol, Avda Puerta Hierro S-N, Madrid 28040, Spain
[4] Univ Complutense Madrid, Inst Univ Invest Neuroquim, Madrid 28040, Spain
[5] Univ Autonoma Madrid, Sch Med, Dept Biochem, Madrid 28040, Spain
[6] Univ Autonoma Madrid, Inst Teofilo Hernando Drug Discovery, Madrid 28029, Spain
[7] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
关键词
tauopathies; oxidative stress; neuroinflammation; neurodegeneration; PiD; CBD; AD; FTLD; DS; ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; PROGRESSIVE SUPRANUCLEAR PALSY; NF-KAPPA-B; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; HEME OXYGENASE-1; MITOCHONDRIAL DYSFUNCTION; GENE-EXPRESSION;
D O I
10.3390/antiox12081564
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
Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular mechanisms that occur as a consequence of aging and transcription factor nuclear factor erythroid-2-related factor 2 (NRF2) and the connection with the TAU protein. We focused on the relevance of NRF2 in the main processes involved in neurodegeneration and associated with aging, such as genomic instability, protein degradation systems (proteasomes/autophagy), cellular senescence, and stem cell exhaustion, as well as inflammation. We also analyzed the effect of aging on TAU protein levels and its aggregation and spread process. Finally, we investigated the interconnection between NRF2 and TAU and the relevance of alterations in the NRF2 signaling pathway in both primary and secondary tauopathies. All these points highlight NRF2 as a possible therapeutic target for tauopathies.
引用
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页数:25
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