Neural regeneration researchOct 29, 2026

How the Sirtuin 1/PGC-1α Pathway Controls Mitochondria and May Help Treat Neurodegenerative Diseases

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

Updated Nov 2, 2026

Abstract

Mitochondrial dysfunction is a central factor in neurodegenerative diseases.

Sirtuin 1 activates peroxisome proliferator-activated receptor gamma coactivator 1α through deacetylation, which is crucial for mitochondrial function.
Activated peroxisome proliferator-activated receptor gamma coactivator 1α regulates processes such as mitochondrial biogenesis and energy metabolism.
Downregulation of the Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1α pathway is frequently observed in neurodegenerative diseases.
Activating this pathway may improve mitochondrial dysfunction and provide neuroprotective effects in preclinical studies.
The article discusses molecular structure and interaction mechanisms to support the development of new drugs targeting this pathway.

Simplified

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.

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How the Sirtuin 1/PGC-1α Pathway Controls Mitochondria and May Help Treat Neurodegenerative Diseases

Abstract

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