Neural Regeneration Research· 2026Q1
Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1α signaling pathway: Molecular mechanisms from mitochondrial function regulation to the treatment of neurodegenerative diseases
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- Q1SCImago
- 2026year
Short summary
Activation of the Sirtuin 1/PGC-1α pathway ameliorates mitochondrial dysfunction and offers neuroprotection in neurodegenerative diseases.
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Key points
- Sirtuin 1 (SIRT1) activates PGC-1α via deacetylation, linking cellular energy status to mitochondrial function.
- Activated PGC-1α regulates key mitochondrial processes including biogenesis, dynamics, autophagy, and antioxidant defense.
- Downregulation of the SIRT1/PGC-1α pathway is observed in neurodegenerative diseases.
- Activating the SIRT1/PGC-1α pathway shows promise in preclinical models for treating mitochondrial dysfunction and neurodegeneration.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Mitochondrial dysfunction is considered a central factor in the onset and progression of various neurodegenerative diseases. Sirtuin 1 is a nicotinamide adenine dinucleotide-dependent deacetylase that senses changes in the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide ratio and activates the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1α through deacetylation. Activated peroxisome proliferator-activated receptor gamma coactivator 1α subsequently interacts with multiple transcription factors to regulate mitochondrial biogenesis, mitochondrial dynamics, autophagy, energy metabolism, and antioxidant defense, thereby playing a critical role in maintaining mitochondrial functional homeostasis. Preclinical studies have shown that neurodegenerative diseases are frequently accompanied by downregulation of the expression or activity of key components of the Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1α pathway, whereas activation of this pathway can ameliorate associated mitochondrial dysfunction and exert neuroprotective effects. This article systematically elucidates the pivotal role of the Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1α pathway in neurodegenerative diseases from the perspectives of molecular structure, interaction mechanisms, and regulation of mitochondrial function, aiming to provide a theoretical foundation for the development of novel multi-target drugs and intervention strategies.
The authors' abstract, as published at the source. Neural Regeneration Research, 2026 · DOI ↗
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Field: Geriatrics and Gerontology
Geriatrics and GerontologyMedicine