{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T10:27:58Z","timestamp":1793960878626,"version":"4.8.0"},"reference-count":127,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>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-1\u03b1). Additionally, it has been observed that PGC-1\u03b1 appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1\u03b1 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-1\u03b1 upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1\u03b1 deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1\u03b1 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-1\u03b1 role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1\u03b1 function in synaptic transmission and neuronal survival.<\/jats:p>","DOI":"10.4103\/1673-5374.317957","type":"journal-article","created":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T11:31:40Z","timestamp":1625916700000},"page":"237-245","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":77,"title":["Deciphering the role of PGC-1\u03b1 in neurological disorders: from mitochondrial dysfunction to synaptic failure"],"prefix":"10.4103","volume":"17","author":[{"given":"Jessica D.","family":"Panes","sequence":"first","affiliation":[{"name":"Laboratorio de Screening de Compuestos Neuroactivos (LSCN), Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Wendt","sequence":"additional","affiliation":[{"name":"Laboratorio de Screening de Compuestos Neuroactivos (LSCN), Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Ramirez-Molina","sequence":"additional","affiliation":[{"name":"Laboratorio de Screening de Compuestos Neuroactivos (LSCN), Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio A.","family":"Castro","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-8102","authenticated-orcid":false,"given":"Jorge","family":"Fuentealba","sequence":"additional","affiliation":[{"name":"Laboratorio de Screening de Compuestos Neuroactivos (LSCN), Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"},{"name":"Centro de Investigaciones Avanzadas en Biomedicina (CIAB-UdeC), Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"R1-20260525","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.celrep.2015.12.043","article-title":"Deposition of 5-methylcytosine on enhancer RNAs enables the coactivator function of PGC-1\u03b1","volume":"14","author":"Aguilo","year":"2016","journal-title":"Cell Rep"},{"key":"R2-20260525","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1474-9726.2007.00357.x","article-title":"Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response","volume":"7","author":"Anderson","year":"2008","journal-title":"Aging Cell"},{"key":"R3-20260525","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes","volume":"72","author":"Anon","year":"1993","journal-title":"Cell"},{"key":"R4-20260525","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1038\/ncomms4569","article-title":"Morphological and functional remodelling of the neuromuscular junction by skeletal muscle PGC-1\u03b1","volume":"5","author":"Arnold","year":"2014","journal-title":"Nat Commun"},{"key":"R5-20260525","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1080\/15384101.2016.1237170","article-title":"Nucleus or cytoplasm? 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