{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:16:20Z","timestamp":1790090180588,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","award":["0086407"],"award-info":[{"award-number":["0086407"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","award":["GM119160"],"award-info":[{"award-number":["GM119160"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ESPCI Paris","award":["0086407"],"award-info":[{"award-number":["0086407"]}]},{"name":"ESPCI Paris","award":["GM119160"],"award-info":[{"award-number":["GM119160"]}]},{"name":"NIH\/NIGMS","award":["0086407"],"award-info":[{"award-number":["0086407"]}]},{"name":"NIH\/NIGMS","award":["GM119160"],"award-info":[{"award-number":["GM119160"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson disease (PD) is a common neurodegenerative condition affecting people predominantly at old age that is characterized by a progressive loss of midbrain dopaminergic neurons and by the accumulation of \u03b1-synuclein-containing intraneuronal inclusions known as Lewy bodies. Defects in cellular degradation processes such as the autophagy-lysosomal pathway are suspected to be involved in PD progression. The mammalian Lysosomal-associated membrane proteins LAMP1 and LAMP2 are transmembrane glycoproteins localized in lysosomes and late endosomes that are involved in autophagosome\/lysosome maturation and function. Here, we show that the lack of Drosophila Lamp1, the homolog of LAMP1 and LAMP2, severely increased fly susceptibility to paraquat, a pro-oxidant compound known as a potential PD inducer in humans. Moreover, the loss of Lamp1 also exacerbated the progressive locomotor defects induced by the expression of PD-associated mutant \u03b1-synuclein A30P (\u03b1-synA30P) in dopaminergic neurons. Remarkably, the ubiquitous re-expression of Lamp1 in a mutant context fully suppressed all these defects and conferred significant resistance towards both PD factors above that of wild-type flies. Immunostaining analysis showed that the brain levels of \u03b1-synA30P were unexpectedly decreased in young adult Lamp1-deficient flies expressing this protein in comparison to non-mutant controls. This suggests that Lamp1 could neutralize \u03b1-synuclein toxicity by promoting the formation of non-pathogenic aggregates in neurons. Overall, our findings reveal a novel role for Drosophila Lamp1 in protecting against oxidative stress and \u03b1-synuclein neurotoxicity in PD models, thus furthering our understanding of the function of its mammalian homologs.<\/jats:p>","DOI":"10.3390\/ijms232113078","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T04:57:34Z","timestamp":1667105854000},"page":"13078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Lamp1 Deficiency Enhances Sensitivity to \u03b1-Synuclein and Oxidative Stress in Drosophila Models of Parkinson Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Zohra","family":"Rahmani","sequence":"first","affiliation":[{"name":"Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, UMR 8249, CNRS, ESPCI Paris, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya","family":"Surabhi","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2332-8423","authenticated-orcid":false,"given":"Francisca","family":"Rojo-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, UMR 8249, CNRS, ESPCI Paris, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Dulac","sequence":"additional","affiliation":[{"name":"Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, UMR 8249, CNRS, ESPCI Paris, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Jenny","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, NY 10461, USA"},{"name":"Department of Genetics, Albert Einstein College of Medicine, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-454X","authenticated-orcid":false,"given":"Serge","family":"Birman","sequence":"additional","affiliation":[{"name":"Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, UMR 8249, CNRS, ESPCI Paris, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00005072-199603000-00001","article-title":"Neuropathology of Parkinson\u2019s disease","volume":"55","author":"Forno","year":"1996","journal-title":"J. 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