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However, the link between lysosomal aberrations and neuronal death is poorly explored. To uncover the functional consequences of lysosomal aberrations in disease pathogenesis, we analyze human dermal fibroblasts from HSP15 patients as well as primary cortical neurons derived from an SPG15 knockout (KO) mouse model. We find that SPG15 protein loss induces defective anterograde transport, impaired neurite outgrowth, axonal swelling and reduced autophagic flux in association with the onset of lysosomal abnormalities. Additionally, we observe lipid accumulation within the lysosomal compartment, suggesting that distortions in cellular lipid homeostasis are intertwined with lysosomal alterations. We further demonstrate that SPG15 KO neurons exhibit synaptic dysfunction, accompanied by augmented vulnerability to glutamate-induced excitotoxicity. Overall, our study establishes an intimate link between lysosomal aberrations, lipid metabolism and electrophysiological impairments, suggesting that lysosomal defects are at the core of multiple neurodegenerative disease processes in HSP15.<\/jats:p>","DOI":"10.1093\/hmg\/ddac063","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T12:12:05Z","timestamp":1647519125000},"page":"2693-2710","source":"Crossref","is-referenced-by-count":15,"title":["SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction"],"prefix":"10.1093","volume":"31","author":[{"given":"Lara","family":"Marrone","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"},{"name":"Department of Neuroscience , Janssen Pharmaceutica, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo M","family":"Marchi","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P","family":"Webster","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Marroccella","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Coldicott","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Academic Unit of Radiology , Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Alves-Cruzeiro","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zih-Liang","family":"Yang","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Higginbottom","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukhran","family":"Khundadze","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics , Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J","family":"Shaw","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics , Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"Livesey","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimoun","family":"Azzouz","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) , Department of Neuroscience, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"2022082420180728600_ref1","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/brain\/aww111","article-title":"Genetic and phenotypic characterization of complex hereditary spastic 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Bull."},{"key":"2022082420180728600_ref42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41531-019-0103-7","article-title":"Parkinson's disease: proteinopathy or lipidopathy?","volume":"6","author":"Fanning","year":"2020","journal-title":"NPJ Parkinsons Dis"},{"key":"2022082420180728600_ref43","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/brain\/awz382","article-title":"Lipid metabolic pathways converge in motor neuron degenerative diseases","volume":"143","author":"Rickman","year":"2020","journal-title":"Brain"},{"key":"2022082420180728600_ref44","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ajhg.2007.10.001","article-title":"Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration","volume":"82","author":"Tsaousidou","year":"2008","journal-title":"Am. J. Hum. 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