FASEB journal : official publication of the Federation of American Societies for Experimental BiologySep 9, 2026

SIRT1's Role, Importance, and Treatment Potential in Brain Degenerative Diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 10, 2026

Abstract

Sirtuin 1 (SIRT1) is associated with cognitive resilience and may play a critical role in neurodegenerative diseases.

Neurodegenerative diseases involve protein aggregation, mitochondrial dysfunction, and cognitive decline.
SIRT1 is linked to stress adaptation, protein maintenance, and metabolic balance in relation to disease progression.
Evidence suggests that reduced or dysregulated SIRT1 may contribute to cognitive impairment in Alzheimer's disease, Parkinson's disease, and Huntington's disease.
The effects of SIRT1 on neurodegeneration may vary depending on the specific disease and its progression stage.
Potential therapeutic strategies targeting SIRT1 are evaluated for their opportunities and limitations in addressing cognitive decline.

Simplified

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.

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SIRT1's Role, Importance, and Treatment Potential in Brain Degenerative Diseases

Abstract

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