{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:10:15Z","timestamp":1790795415326,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie Sk\u0142odowska-Curie","award":["746509"],"award-info":[{"award-number":["746509"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The accumulation and aggregation of \u03b1-synuclein (\u03b1-SYN) is a common characteristic of synucleinopathies, such as Parkinson\u2019s Disease (PD), Dementia with Lewy Bodies (DLB) or Multiple System Atrophy (MSA). Multiplications of the wildtype gene of \u03b1-SYN (SNCA) and most point mutations make \u03b1-SYN more aggregate-prone, and are associated with mitochondrial defects, trafficking obstruction, and impaired proteostasis, which contribute to elevated neuronal death. Here, we present new zebrafish models expressing either human wildtype (wt), or A53T mutant, \u03b1-SYN that recapitulate the above-mentioned hallmarks of synucleinopathies. The appropriate clearance of toxic \u03b1-SYN has been previously shown to play a key role in maintaining cell homeostasis and survival. However, the paucity of models to investigate \u03b1-SYN degradation in vivo limits our understanding of this process. Based on our recently described imaging method for measuring tau protein clearance in neurons in living zebrafish, we fused human SNCA to the photoconvertible protein Dendra2 which enabled analyses of wt and A53T \u03b1-SYN clearance kinetics in vivo. Moreover, these zebrafish models can be used to investigate the kinetics of \u03b1-SYN aggregation and to study the mechanisms, and potential new targets, controlling the clearance of both soluble and aggregated \u03b1-SYN.<\/jats:p>","DOI":"10.3390\/genes13050868","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T21:46:53Z","timestamp":1652392013000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A New Zebrafish Model to Measure Neuronal \u03b1-Synuclein Clearance In Vivo"],"prefix":"10.3390","volume":"13","author":[{"given":"Ana","family":"Lopez","sequence":"first","affiliation":[{"name":"Cambridge Institute for Medical Research, Cambridge Biomedical Campus, The Keith Peters Building Cambridge, Hills Road, Cambridge CB2 0XY, UK"},{"name":"UK Dementia Research Institute, Cambridge Biomedical Campus, The Keith Peters Building Cambridge, Hills Road, Cambridge CB2 0XY, UK"},{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Gorb","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Palha","sequence":"additional","affiliation":[{"name":"Neuroscience and Immunoinflammation Therapeutic Area, Institut de Recherche Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3721-7126","authenticated-orcid":false,"given":"Angeleen","family":"Fleming","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, Cambridge Biomedical Campus, The Keith Peters Building Cambridge, Hills Road, Cambridge CB2 0XY, UK"},{"name":"UK Dementia Research Institute, Cambridge Biomedical Campus, The Keith Peters Building Cambridge, Hills Road, Cambridge CB2 0XY, UK"},{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Rubinsztein","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, Cambridge Biomedical Campus, The Keith Peters Building Cambridge, Hills Road, Cambridge CB2 0XY, UK"},{"name":"UK Dementia Research Institute, Cambridge Biomedical Campus, The Keith Peters Building Cambridge, Hills Road, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/jnc.14810","article-title":"The physiological role of alpha-synuclein and its relationship to Parkinson\u2019s Disease","volume":"150","author":"Sulzer","year":"2019","journal-title":"J. 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