{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:14:47Z","timestamp":1769091287226,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS118177"],"award-info":[{"award-number":["R01NS118177"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Mutations of the SPAST gene that encodes the microtubule-severing enzyme called spastin are the chief cause of Hereditary Spastic Paraplegia. Growing evidence indicates that pathogenic mutations functionally compromise the spastin protein and endow it with toxic gain-of-function properties. With each of these two factors potentially relevant to disease etiology, the present article discusses possible therapeutic strategies that may ameliorate symptoms in patients suffering from SPAST-based Hereditary Spastic Paraplegia, which is usually termed SPG4-HSP.<\/jats:p>","DOI":"10.3390\/brainsci11081081","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:54:35Z","timestamp":1629284075000},"page":"1081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Therapeutic Strategies for Mutant SPAST-Based Hereditary Spastic Paraplegia"],"prefix":"10.3390","volume":"11","author":[{"given":"Neha","family":"Mohan","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19422, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19422, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6059-5518","authenticated-orcid":false,"given":"Gerardo","family":"Morfini","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter W.","family":"Baas","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19422, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1136\/jnnp.69.2.150","article-title":"Hereditary spastic paraparesis: A review of new developments","volume":"69","author":"McDermott","year":"2000","journal-title":"J. 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