review · Sci
A systematic review of eleven preclinical studies examined the role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, known as PGC-1α, in type 2 diabetes and neurodegenerative diseases. The protein regulates mitochondrial biogenesis, energy balance, and metabolism. Evidence shows that reduced PGC-1α signalling is linked to mitochondrial dysfunction, oxidative stress, impaired glucose metabolism, insulin resistance, and neurodegeneration across several molecular pathways. Both exercise and pharmacological interventions were found to boost PGC-1α signalling in laboratory models, potentially restoring mitochondrial health, aiding metabolism, and supporting neuronal survival. Although reviewed studies generally demonstrated a low risk of bias, high heterogeneity and methodological limitations were common. PGC-1α serves as a significant molecular link between metabolic failure and neurodegeneration, but robust translational and clinical validation remains essential before these mechanisms can be confirmed in humans.
Type 2 diabetes and neurodegenerative conditions represent major health challenges that share underlying cellular defects. By highlighting PGC-1α as a common bridge between energy metabolism and brain health, this research helps clarify how metabolic dysfunction drives neuronal damage. Understanding these shared pathways could aid the development of unified therapeutic approaches and lifestyle strategies focused on preserving mitochondrial function.
This research could inform early-stage discovery programmes for pharmaceutical developers seeking drug targets that address metabolic disorders and neurodegeneration simultaneously. Because the evidence is derived entirely from preclinical cell and animal models with documented methodological limitations, the work is at an early research stage and remains distant from real-world clinical or market use until extensive translational trials are conducted.
AI-generated from the published abstract. Always read the original work before citing.
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), encoded by PPARGC1A, plays an important role in the regulation of mitochondrial biogenesis, metabolism, and energy balance. Alterations in PGC-1α function have been found in type 2 diabetes mellitus (T2DM) and neurodegenerative diseases (NDs), but molecular similarities in these pathologies have not been comprehensively studied yet. The current systematic review provides a synthesis of preclinical data on the role of PGC-1α in relation to T2DM and NDs. This study was performed in accordance with the PRISMA 2020 statement. PubMed, Scopus, Web of Science and ScienceDirect were screened for studies published between January 2015 and March 2025. Preclinical studies, including in vivo animal studies with and without in vitro studies, were evaluated for risk of bias according to the SYRCLE checklist and modified CAMARADES checklist. Due to the high heterogeneity, data were qualitatively synthesized. Eleven preclinical studies met the inclusion criteria. Decreased PGC-1α signalling was indicated to be linked to mitochondrial dysfunction, oxidative stress, glucose metabolism impairment, insulin resistance and neurodegeneration via AMPK, SIRT1, CREB, FOXO, PPARγ, Parkin/PARIS, and BDNF pathways. Pharmacological interventions and exercise support increased PGC-1α signalling, potentially improved mitochondrial functions and metabolism and facilitated neuronal survival. Though most studies had a low risk of bias, methodological limitations were quite prevalent. PGC-1α is a key molecular mediator between metabolic dysfunction and neurodegeneration and is a potential target for intervention. However, more rigorous translational and clinical studies are required for the validation of results. This systematic review has not been prospectively registered.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.3390/sci8080211
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
