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Deciphering the role of PGC-1α in neurological disorders: from mitochondrial dysfunction to synaptic failure.

Abstract：

:The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas (hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1α function in synaptic transmission and neuronal survival.

journal_name

Neural Regen Res

journal_title

Neural regeneration research

authors

Panes JD,Wendt A,Ramirez-Molina O,Castro PA,Fuentealba J

doi

10.4103/1673-5374.317957

keywords:

["Alzheimer’s disease","Huntington’s disease","PGC-1α","Parkinson’s disease","amyotrophic lateral sclerosis","mitochondrial dysfunction","synaptic function","vascular dementia"]

subject

Has Abstract

pub_date

2022-02-01 00:00:00

pages

237-245

issue

2

eissn

1673-5374

issn

1876-7958

pii

NeuralRegenRes_2022_17_2_237_317957

journal_volume

17

pub_type

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