SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.

Authors

Jiabin Duan, Jiaqi Liu, Qingsheng Meng, Jiahao Liu, Sitian Yang, Fang Zhou, Jing Cao

Published in

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 17. Pages e72288. Sep 15, 2026.

Abstract

Neurodegenerative diseases are characterized by progressive protein aggregation, mitochondrial dysfunction, neuroinflammation, and cognitive decline, yet effective mechanism-based interventions remain limited. Sirtuin 1 (SIRT1), an NAD⁺-dependent deacetylase, has emerged as a multifunctional regulator linking stress adaptation, proteostasis, and metabolic homeostasis to disease progression. Increasing evidence indicates that SIRT1 supports cognitive resilience by coordinating synaptic plasticity, autophagy-lysosomal function, mitochondrial homeostasis, and inflammatory control. In Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), reduced or dysregulated SIRT1 is associated with protein aggregation, mitochondrial dysfunction, and cognitive decline, although its effects may be disease- and stage-dependent, particularly in HD. This review summarizes the structural and catalytic features of SIRT1, examines the mechanisms linking SIRT1 to cognitive impairment across major neurodegenerative diseases, and evaluates the opportunities and limitations of SIRT1-targeted therapeutic strategies.

PMID:
42714849
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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