Deciphering the role of PGC-1α in neurological disorders: from mitochondrial dysfunction to synaptic failure
Jessica D.Panes1
Aline Wendt1
Oscar Ramirez-Molina1
Patricio A.Castro2
Jorge Fuentealba3
1.Laboratorio de Screening de Compuestos Neuroactivos(LSCN),Departamento de Fisiología,Facultad de Ciencias Biológicas,Universidad de Concepción,Concepción,Chile2.Departamento de Fisiología,Facultad de Ciencias Biológicas,Universidad de Concepción,Concepción,Chile3.Laboratorio de Screening de Compuestos Neuroactivos(LSCN),Departamento de Fisiología,Facultad de Ciencias Biológicas,Universidad de Concepción,Concepción,Chile;Centro de Investigaciones Avanzadas en Biomedicina(CIAB-UdeC),Facultad de Ciencias Biológicas,Universidad de Concepción,Concepción,Chile
摘要：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-1αdownregulation 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.
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论文发表日期：2022-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 237-245 )
英文信息