Title:Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated
Pathways in Neurodegenerative Diseases: Molecular Insights and Potential
Therapeutic Applications
Volume: 21
Issue: 5
Author(s): Abdullah Shaito, Maryam Al-Mansoob, Salma M.S. Ahmad, Mohammad Z. Haider, Ali H. Eid, Anna Maria Posadino, Gianfranco Pintus*Roberta Giordo
Affiliation:
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
- Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research,
University of Sharjah, University City Rd, Sharjah, 27272, United Arab Emirates
Keywords:
Resveratrol, neurodegenerative diseases, mitochondria, mitochondrial biogenesis, polyphenols, central nervous system.
Abstract: Neurodegenerative disorders include different neurological conditions that affect nerve
cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination,
and mental functioning. The molecular mechanisms underpinning neurodegenerative disease
pathogenesis are still unclear. Nonetheless, there is experimental evidence to demonstrate that the perturbation
of mitochondrial function and dynamics play an essential role. In this context, mitochondrial
biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number,
plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic
activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell
division and variations in energy demand in response to extracellular stimuli; therefore, it may represent
a promising therapeutic target for developing new curative approaches to prevent or counteract
neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have been
proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally
occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various
tissues, including the nervous tissue, and an ever-growing number of studies highlight its neurotherapeutic
potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant
and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria
biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT,
TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning
the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in
the context of neurodegenerative diseases.