{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:28:54Z","timestamp":1791246534931,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801256"],"award-info":[{"award-number":["81801256"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Peroxisome proliferator\u2010activated receptor gamma coactivator 1\u2010alpha (PGC\u20101\u03b1) is a key regulator of mitochondrial biogenesis and antioxidative defenses, and it may play a critical role in Parkinson's disease (PD). F\u2010box\/WD repeat domain\u2010containing protein (FBXW7), an E3 protein ligase, promotes the degradation of substrate proteins through the ubiquitin\u2010proteasome system (UPS) and leads to the clearance of PGC\u20101\u03b1. Here, we elucidate a novel post\u2010translational mechanism for regulating PGC\u20101\u03b1 levels in neurons. We show that enhancing chaperone\u2010mediated autophagy (CMA) activity promotes the CMA\u2010mediated degradation of FBXW7 and consequently increases PGC\u20101\u03b1. We confirm the relevance of this pathway\n                    <jats:italic>in vivo<\/jats:italic>\n                    by showing decreased FBXW7 and increased PGC\u20101\u03b1 as a result of boosting CMA selectively in dopaminergic (DA) neurons by overexpressing lysosomal\u2010associated membrane protein 2A (LAMP2A) in TH\u2010Cre\u2010LAMP2\u2010loxp conditional mice. We further demonstrate that these mice are protected against MPTP\u2010induced oxidative stress and neurodegeneration. These results highlight a novel regulatory pathway for PGC\u20101\u03b1 in DA neurons and suggest targeted increasing of CMA or decreasing FBXW7 in DA neurons as potential neuroprotective strategies in PD.\n                  <\/jats:p>","DOI":"10.1111\/febs.17276","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T05:15:48Z","timestamp":1729487748000},"page":"332-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>PGC<\/scp>\n                    \u20101\u03b1 regulation by\n                    <scp>FBXW7<\/scp>\n                    through a novel mechanism linking chaperone\u2010mediated autophagy and the ubiquitin\u2010proteasome system"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6391-2037","authenticated-orcid":false,"given":"Simona","family":"Eleuteri","sequence":"first","affiliation":[{"name":"Department of Neurology, Beth 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Beth Israel Deaconess Medical Center Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston MA 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