{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:05:55Z","timestamp":1788055555310,"version":"build-2784847793"},"reference-count":47,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001790","name":"Ara Parseghian Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001790","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Genetics and Metabolism"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1016\/j.ymgme.2021.11.008","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T12:27:36Z","timestamp":1637065656000},"page":"330-336","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"title":["Reduction of glutamate neurotoxicity: A novel therapeutic approach for Niemann-Pick disease, type C1"],"prefix":"10.1016","volume":"134","author":[{"given":"Antony","family":"Cougnoux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Yerger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason","family":"Fellmeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Serra-Vinardell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Navid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Wassif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh X.","family":"Cawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymgme.2021.11.008_bb0005","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"Vanier","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0010","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/gim.2015.25","article-title":"High incidence of unrecognized visceral\/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets","volume":"18","author":"Wassif","year":"2016","journal-title":"Genet. Med."},{"issue":"5","key":"10.1016\/j.ymgme.2021.11.008_bb0015","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1074\/jbc.TM118.004165","article-title":"NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes","volume":"294","author":"Pfeffer","year":"2019","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00005792-195802000-00001","article-title":"Niemann-Pick disease: a review of eighteen patients","volume":"37","author":"Crocker","year":"1958","journal-title":"Medicine (Baltimore)"},{"issue":"4","key":"10.1016\/j.ymgme.2021.11.008_bb0025","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ymgme.2019.02.004","article-title":"Evaluation of age of death in Niemann-Pick disease, type C: utility of disease support group websites to understand natural history","volume":"126","author":"Bianconi","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2021.11.008_bb0030","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/jimd.12245","article-title":"Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: a large retrospective observational study","volume":"43","author":"Patterson","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0035","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13023-020-01363-2","article-title":"Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease type C: a final report of the NPC registry","volume":"15","author":"Patterson","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.ymgme.2021.11.008_bb0040","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1001\/jamaneurol.2020.3241","article-title":"Association of miglustat with swallowing outcomes in Niemann-Pick disease, type C1","volume":"77","author":"Solomon","year":"2020","journal-title":"JAMA Neurol."},{"issue":"6","key":"10.1016\/j.ymgme.2021.11.008_bb0045","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0301-0082(03)00114-X","article-title":"Patterned Purkinje cell death in the cerebellum","volume":"70","author":"Sarna","year":"2003","journal-title":"Prog. Neurobiol."},{"issue":"2","key":"10.1016\/j.ymgme.2021.11.008_bb0050","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/BF00227765","article-title":"Cerebellar degeneration in the Niemann-Pick type C mouse","volume":"85","author":"Higashi","year":"1993","journal-title":"Acta Neuropathol."},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0055","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21010292","article-title":"Identification of novel pathways associated with patterned cerebellar purkinje neuron degeneration in Niemann-Pick disease, type C1","volume":"21","author":"Martin","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"15","key":"10.1016\/j.ymgme.2021.11.008_bb0060","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1093\/hmg\/ddy169","article-title":"Loss of cerebellar glutamate transporters EAAT4 and GLAST differentially affects the spontaneous firing pattern and survival of Purkinje cells","volume":"27","author":"Perkins","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymgme.2021.11.008_bb0065","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0079-6123(04)48029-7","article-title":"Don't get too excited: mechanisms of glutamate-mediated Purkinje cell death","volume":"148","author":"Slemmer","year":"2005","journal-title":"Prog. Brain Res."},{"issue":"28","key":"10.1016\/j.ymgme.2021.11.008_bb0070","doi-asserted-by":"crossref","first-page":"7438","DOI":"10.1073\/pnas.1617330114","article-title":"Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells","volume":"114","author":"Miyazaki","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"4","key":"10.1016\/j.ymgme.2021.11.008_bb0075","first-page":"929","article-title":"EAAT4, a glutamate transporter with properties of a chloride channel, is predominantly localized in Purkinje cell dendrites, and forms parasagittal compartments in rat cerebellum","volume":"78","author":"Nagao","year":"1997","journal-title":"Neuroscience"},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0080","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/jnr.490380103","article-title":"Involvement of glutamate receptors, lipases, and phospholipases in long-term potentiation and neurodegeneration","volume":"38","author":"Farooqui","year":"1994","journal-title":"J. Neurosci. Res."},{"issue":"2","key":"10.1016\/j.ymgme.2021.11.008_bb0085","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00424-010-0809-1","article-title":"Glutamate receptors, neurotoxicity and neurodegeneration","volume":"460","author":"Lau","year":"2010","journal-title":"Pflugers Arch."},{"issue":"9","key":"10.1016\/j.ymgme.2021.11.008_bb0090","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1523\/JNEUROSCI.14-09-05559.1994","article-title":"Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex","volume":"14","author":"Arriza","year":"1994","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ymgme.2021.11.008_bb0095","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/bs.apha.2016.01.004","article-title":"Transcriptional regulation of glutamate transporters: from extracellular signals to transcription factors","volume":"76","author":"Martinez-Lozada","year":"2016","journal-title":"Adv. Pharmacol."},{"issue":"15","key":"10.1016\/j.ymgme.2021.11.008_bb0100","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21155368","article-title":"Single cell transcriptome analysis of Niemann-Pick disease, type C1 cerebella","volume":"21","author":"Cougnoux","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0105","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1038\/s41598-018-21805-z","article-title":"Impact of reduced cerebellar EAAT expression on Purkinje cell firing pattern of NPC1-deficient mice","volume":"8","author":"Rabenstein","year":"2018","journal-title":"Sci. Rep."},{"issue":"3","key":"10.1016\/j.ymgme.2021.11.008_bb0110","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/jhg.2016.137","article-title":"Late-onset episodic ataxia associated with SLC1A3 mutation","volume":"62","author":"Choi","year":"2017","journal-title":"J. Hum. Genet."},{"key":"10.1016\/j.ymgme.2021.11.008_bb0115","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3389\/fnins.2015.00469","article-title":"Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence?","volume":"9","author":"Lewerenz","year":"2015","journal-title":"Front. Neurosci."},{"issue":"5323","key":"10.1016\/j.ymgme.2021.11.008_bb0120","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.277.5323.232","article-title":"Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene","volume":"277","author":"Loftus","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.ymgme.2021.11.008_bb0125","article-title":"A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia","volume":"39","author":"Guyenet","year":"2010","journal-title":"J. Vis. Exp."},{"issue":"12","key":"10.1016\/j.ymgme.2021.11.008_bb0130","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1093\/hmg\/ddy112","article-title":"Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention","volume":"27","author":"Cougnoux","year":"2018","journal-title":"Hum. Mol. Genet."},{"issue":"7","key":"10.1016\/j.ymgme.2021.11.008_bb0135","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"issue":"4","key":"10.1016\/j.ymgme.2021.11.008_bb0140","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ymgme.2018.10.009","article-title":"Necroptosis inhibition as a therapy for Niemann-Pick disease, type C1: inhibition of RIP kinases and combination therapy with 2-hydroxypropyl-beta-cyclodextrin","volume":"125","author":"Cougnoux","year":"2018","journal-title":"Mol. Genet. Metab."},{"issue":"9","key":"10.1016\/j.ymgme.2021.11.008_bb0145","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0006951","article-title":"Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression","volume":"4","author":"Davidson","year":"2009","journal-title":"PLoS One"},{"issue":"7","key":"10.1016\/j.ymgme.2021.11.008_bb0150","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1073\/pnas.0810895106","article-title":"Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-\/- mouse","volume":"106","author":"Liu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"276","key":"10.1016\/j.ymgme.2021.11.008_bb0155","doi-asserted-by":"crossref","first-page":"276ra26","DOI":"10.1126\/scitranslmed.3010101","article-title":"Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease","volume":"7","author":"Vite","year":"2015","journal-title":"Sci. Transl. Med."},{"issue":"10104","key":"10.1016\/j.ymgme.2021.11.008_bb0160","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1016\/S0140-6736(17)31465-4","article-title":"Intrathecal 2-hydroxypropyl-beta-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1\u20132 trial","volume":"390","author":"Ory","year":"2017","journal-title":"Lancet"},{"issue":"10","key":"10.1016\/j.ymgme.2021.11.008_bb0165","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/jcp.22609","article-title":"Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics","volume":"226","author":"Kim","year":"2011","journal-title":"J. Cell. Physiol."},{"issue":"7021","key":"10.1016\/j.ymgme.2021.11.008_bb0170","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nature03180","article-title":"Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression","volume":"433","author":"Rothstein","year":"2005","journal-title":"Nature"},{"issue":"6 Suppl 4","key":"10.1016\/j.ymgme.2021.11.008_bb0175","first-page":"S233","article-title":"The pharmacology and mechanism of action of riluzole","volume":"47","author":"Doble","year":"1996","journal-title":"Neurology"},{"issue":"2\u20133","key":"10.1016\/j.ymgme.2021.11.008_bb0180","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ejphar.2007.10.023","article-title":"Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1","volume":"578","author":"Fumagalli","year":"2008","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.ymgme.2021.11.008_bb0185","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.neuint.2011.10.017","article-title":"Riluzole elevates GLT-1 activity and levels in striatal astrocytes","volume":"60","author":"Carbone","year":"2012","journal-title":"Neurochem. Int."},{"issue":"7","key":"10.1016\/j.ymgme.2021.11.008_bb0190","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.ijdevneu.2013.06.002","article-title":"Riluzole increases glutamate uptake by cultured C6 astroglial cells","volume":"31","author":"Dall'Igna","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"issue":"2","key":"10.1016\/j.ymgme.2021.11.008_bb0195","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0005-2760(89)90200-2","article-title":"Type C Niemann-Pick disease: dimethyl sulfoxide moderates abnormal LDL-cholesterol processing in mutant fibroblasts","volume":"1006","author":"Blanchette Mackie","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"issue":"19","key":"10.1016\/j.ymgme.2021.11.008_bb0200","doi-asserted-by":"crossref","first-page":"13116","DOI":"10.1074\/jbc.M707697200","article-title":"Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes","volume":"283","author":"Lee","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.ymgme.2021.11.008_bb0205","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0006-8993(00)02430-6","article-title":"Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes","volume":"871","author":"Azbill","year":"2000","journal-title":"Brain Res."},{"issue":"3","key":"10.1016\/j.ymgme.2021.11.008_bb0210","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.neuro.2009.02.014","article-title":"Co-treatment with riluzole, a neuroprotective drug, ameliorates the 3-acetylpyridine-induced neurotoxicity in cerebellar Purkinje neurones of rats: behavioural and electrophysiological evidence","volume":"30","author":"Janahmadi","year":"2009","journal-title":"Neurotoxicology"},{"issue":"6","key":"10.1016\/j.ymgme.2021.11.008_bb0215","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1097\/JCP.0000000000000797","article-title":"Riluzole serum concentration in pediatric patients treated for obsessive-compulsive disorder","volume":"37","author":"Grant","year":"2017","journal-title":"J. Clin. Psychopharmacol."},{"issue":"3","key":"10.1016\/j.ymgme.2021.11.008_bb0220","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.nbd.2011.12.027","article-title":"Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann-Pick type C1 mice","volume":"45","author":"Pressey","year":"2012","journal-title":"Neurobiol. Dis."},{"issue":"4","key":"10.1016\/j.ymgme.2021.11.008_bb0225","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1002\/pmic.200500412","article-title":"Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis","volume":"6","author":"Byun","year":"2006","journal-title":"Proteomics"},{"key":"10.1016\/j.ymgme.2021.11.008_bb0230","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2011.04.020","article-title":"Glutamatergic neurotransmission in a mouse model of Niemann-Pick type C disease","volume":"1396","author":"D'Arcangelo","year":"2011","journal-title":"Brain Res."},{"issue":"3","key":"10.1016\/j.ymgme.2021.11.008_bb0235","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1093\/cercor\/bhz179","article-title":"Stimulation of mGluR1\/5 improves defective internalization of AMPA receptors in NPC1 mutant mouse","volume":"30","author":"Feng","year":"2020","journal-title":"Cereb. Cortex"}],"container-title":["Molecular Genetics and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S109671922100826X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S109671922100826X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T23:51:17Z","timestamp":1761090677000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S109671922100826X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["S109671922100826X"],"URL":"https:\/\/doi.org\/10.1016\/j.ymgme.2021.11.008","relation":{},"ISSN":["1096-7192"],"issn-type":[{"value":"1096-7192","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Reduction of glutamate neurotoxicity: A novel therapeutic approach for Niemann-Pick disease, type C1","name":"articletitle","label":"Article Title"},{"value":"Molecular Genetics and Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymgme.2021.11.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}