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Mitochondrial insufficiency forms a significant feature of the pathology of this disease, yet studies attempting to address this are rare. The working hypothesis is that mitochondria become overloaded with cholesterol which renders them dysfunctional. We examined two potential protein targets\u2014translocator protein (TSPO) and steroidogenic acute regulatory protein D1 (StARD1)\u2014which are implicated in cholesterol transport to mitochondria, in addition to glucocerbrosidase 2 (GBA2), the target of miglustat, which is currently the only approved treatment for NPCD. However, inhibiting these proteins did not correct the mitochondrial defect in NPC1\u2010deficient cells.<\/jats:p>","DOI":"10.1002\/1873-3468.14802","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T21:25:06Z","timestamp":1706822706000},"page":"477-484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondrial dysfunction in\n                    <scp>NPC1<\/scp>\n                    \u2010deficiency is not rescued by drugs targeting the glucosylceramidase\n                    <scp>GBA2<\/scp>\n                    and the cholesterol\u2010binding proteins\n                    <scp>TSPO<\/scp>\n                    and\n                    <scp>StARD1<\/scp>"],"prefix":"10.1002","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-8648","authenticated-orcid":false,"given":"Simon","family":"Wheeler","sequence":"first","affiliation":[{"name":"Leicester School of Pharmacy De Montfort University  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Leicester School of Pharmacy De Montfort University  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-9440","authenticated-orcid":false,"given":"Victor","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Atomwise  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M. 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