{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:36:43Z","timestamp":1792460203769,"version":"4.5.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder caused by loss-of-function mutations in the\n                    <jats:italic>NPC1<\/jats:italic>\n                    gene. NPC1 deficit primarily disrupts lipid homeostasis and subsequently drives cellular degeneration through mechanisms involving impaired autophagy and mitophagy, mitochondrial dysfunction, and, recently demonstrated NAD depletion that links autophagy impairment to neuronal death. Emerging evidence also highlights the activation of innate immune signaling leading to neuroinflammation. In this review, we synthesize current mechanistic insights and describe how these molecular deficits are interconnected to drive neuronal death in NPC1 disease. We also discuss how these pathological processes parallel those observed in major age-related neurodegenerative pathologies such as Alzheimer\u2019s and Parkinson\u2019s disease. Finally, we highlight emerging therapeutic strategies that can potentially ameliorate these cellular deficits, offering avenues for mitigating neurodegeneration in NPC1 disease and other related neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1857866","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:44:31Z","timestamp":1779083071000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["From autophagy\u2013lysosomal deficits to neurodegeneration in Niemann-Pick type C1 disease: implications for age-related neurodegenerative disorders"],"prefix":"10.3389","volume":"20","author":[{"given":"Yuki","family":"Kawachi","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Medicine, University of Tsukuba","place":["Tsukuba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Kocak","sequence":"additional","affiliation":[{"name":"Department of Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Edgbaston","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor I.","family":"Korolchuk","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Biosciences Institute, Newcastle University","place":["Newcastle upon Tyne, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"Kataura","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Medicine, University of Tsukuba","place":["Tsukuba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sovan","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Edgbaston","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"eady9811","DOI":"10.1126\/sciadv.ady9811","article-title":"NAD(+) reverses Alzheimer's neurological deficits via regulating differential alternative RNA splicing of EVA1C","volume":"11","author":"Ai","year":"2025","journal-title":"Sci. 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