{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:16:19Z","timestamp":1790946979744,"version":"4.1.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T00:00:00Z","timestamp":1624665600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000861","name":"Sparks","doi-asserted-by":"publisher","award":["14CAM03"],"award-info":[{"award-number":["14CAM03"]}],"id":[{"id":"10.13039\/501100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000861","name":"Sparks","doi-asserted-by":"publisher","award":["IS-BRC-1215-20014"],"award-info":[{"award-number":["IS-BRC-1215-20014"]}],"id":[{"id":"10.13039\/501100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Krabbe disease, an inherited leukodystrophy, is a sphingolipidosis caused by deficiency of \u03b2-galactocerebrosidase: it is characterized by myelin loss, and pathological activation of macrophage\/microglia and astrocytes. To define driving pathogenic factors, we explored the expression repertoire of candidate neuroinflammatory genes: upregulation of receptor interacting protein kinase 1 (Ripk1) and disease-associated microglia (DAM) genes, including Cst7 and Ch25h, correlated with severity of Krabbe disease genetically modelled in the twitcher mouse. Upregulation of Ripk1 in Iba1\/Mac2-positive microglia\/macrophage associated with the pathognomic hypertrophic\/globoid phenotype of this disease. Widespread accumulation of ubiquitinin1 in white and grey matter co-localised with p62. In Sandhoff disease, another sphingolipid disorder, neuroinflammation, accumulation of p62 and increased Ripk1 expression was observed. The upregulated DAM genes and macrophage\/microglia expression of Ripk1 in the authentic model of Krabbe disease strongly resemble those reported in Alzheimer disease associating with disturbed autophagosomal\/lysosomal homeostasis. Activation of this shared molecular repertoire, suggests the potential for therapeutic interdiction at a common activation step, irrespective of proximal causation. To clarify the role of Ripk1 in the pathogenesis of Krabbe disease, we first explored the contribution of its kinase function, by intercrossing twitcher and the K45A kinase-dead Ripk1 mouse and breeding to homozygosity. Genetic ablation of Ripk1 kinase activity neither altered the neuropathological features nor the survival of twitcher mice. We conclude that Ripk1 kinase-dependent inflammatory and degenerative capabilities play no instrumental role in Krabbe disease; however, putative kinase-independent functions of Ripk1 remain formally to be explored in its molecular pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddab159","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T19:13:27Z","timestamp":1624389207000},"page":"2082-2099","source":"Crossref","is-referenced-by-count":7,"title":["Expression of Ripk1 and DAM genes correlates with severity and progression of Krabbe disease"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-2527","authenticated-orcid":false,"given":"Mar\u00eda B","family":"Cach\u00f3n-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Level 5, PO Box 157, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Level 5, PO Box 157, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"2021110209345942500_ref1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1073\/pnas.66.2.302","article-title":"Globoid cell leucodystrophy (Krabbe's disease): deficiency of galactocerebroside beta-galactosidase","volume":"66","author":"Suzuki","year":"1970","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021110209345942500_ref2","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1093\/hmg\/10.11.1191","article-title":"A mutation in the saposin A domain of the sphingolipid activator protein (prosaposin) gene results in a late-onset, chronic form of globoid cell leukodystrophy in the mouse","volume":"10","author":"Matsuda","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"2021110209345942500_ref3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.cellbio.21.122303.120013","article-title":"Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids","volume":"21","author":"Kolter","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021110209345942500_ref4","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ymgme.2004.10.004","article-title":"A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans","volume":"84","author":"Spiegel","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"2021110209345942500_ref5","first-page":"3669","volume-title":"Metabolic and Molecular Basis of Inherited Disease","author":"Wenger","year":"2001"},{"key":"2021110209345942500_ref6","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/0006-291X(72)90381-6","article-title":"Globoid cell leukodystrophy: additional deficiency of psychosine galactosidase","volume":"48","author":"Miyatake","year":"1972","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021110209345942500_ref7","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/0006-291X(73)90715-8","article-title":"Deficiency of monogalactosyl diglyceride beta-B-galactosidase activity in krabbe's disease","volume":"53","author":"Wenger","year":"1973","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021110209345942500_ref8","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1073\/pnas.71.3.854","article-title":"Globoid cell leukodystrophy: deficiency of lactosyl ceramide beta-galactosidase","volume":"71","author":"Wenger","year":"1974","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021110209345942500_ref9","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1046\/j.1471-4159.1995.65052267.x","article-title":"The UDP-galactose:ceramide galactosyltransferase: expression pattern in oligodendrocytes and Schwann cells during myelination and substrate preference for hydroxyceramide","volume":"65","author":"Schaeren-Wiemers","year":"1995","journal-title":"J. Neurochem."},{"key":"2021110209345942500_ref10","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1126\/science.6719111","article-title":"Progressive accumulation of toxic metabolite in a genetic leukodystrophy","volume":"224","author":"Igisu","year":"1984","journal-title":"Science"},{"key":"2021110209345942500_ref11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0022-2275(20)39839-4","article-title":"Krabbe disease: a galactosylsphingosine (psychosine) lipidosis","volume":"21","author":"Svennerholm","year":"1980","journal-title":"J. Lipid Res."},{"key":"2021110209345942500_ref12","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1097\/00005072-199309000-00007","article-title":"Effects of psychosine (galactosylsphingosine) on the survival and the fine structure of cultured Schwann cells","volume":"52","author":"Tanaka","year":"1993","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2021110209345942500_ref13","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1097\/00005072-199906000-00009","article-title":"An apoptotic depletion of oligodendrocytes in the twitcher, a murine model of globoid cell leukodystrophy","volume":"58","author":"Taniike","year":"1999","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2021110209345942500_ref14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0304-3940(02)00655-9","article-title":"Apoptotic positive cells in Krabbe brain and induction of apoptosis in rat C6 glial cells by psychosine","volume":"330","author":"Jatana","year":"2002","journal-title":"Neurosci. Lett."},{"key":"2021110209345942500_ref15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neulet.2003.12.126","article-title":"Psychosine-induced apoptosis in a mouse oligodendrocyte progenitor cell line is mediated by caspase activation","volume":"358","author":"Zaka","year":"2004","journal-title":"Neurosci. Lett."},{"key":"2021110209345942500_ref16","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0006-8993(80)90159-6","article-title":"The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease)","volume":"202","author":"Kobayashi","year":"1980","journal-title":"Brain Res."},{"key":"2021110209345942500_ref17","doi-asserted-by":"crossref","first-page":"20097","DOI":"10.1073\/pnas.1912108116","article-title":"Genetic ablation of acid ceramidase in Krabbe disease confirms the psychosine hypothesis and identifies a new therapeutic target","volume":"116","author":"Li","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021110209345942500_ref18","doi-asserted-by":"publisher","first-page":"5356","DOI":"10.1038\/s41467-020-19179-w","article-title":"Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease","volume":"11","author":"Weinstock","year":"2020","journal-title":"Nat. Commun."},{"key":"2021110209345942500_ref19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.neuron.2020.03.031","article-title":"Macrophages expressing GALC improve peripheral Krabbe disease by a mechanism independent of cross-correction","volume":"107","author":"Weinstock","year":"2020","journal-title":"Neuron"},{"key":"2021110209345942500_ref20","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1523\/JNEUROSCI.6344-10.2011","article-title":"Macrophages counteract demyelination in a mouse model of globoid cell leukodystrophy","volume":"31","author":"Kondo","year":"2011","journal-title":"J. Neurosci."},{"key":"2021110209345942500_ref21","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer's disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"2021110209345942500_ref22","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s40478-018-0612-3","article-title":"Glycoprotein NMB: a novel Alzheimer's disease associated marker expressed in a subset of activated microglia","volume":"6","author":"H\u00fcttenrauch","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"2021110209345942500_ref23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00401-015-1388-1","article-title":"TREM2 regulates microglial cell activation in response to demyelination in vivo","volume":"129","author":"Cantoni","year":"2015","journal-title":"Acta Neuropathol."},{"key":"2021110209345942500_ref24","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.yexcr.2004.03.048","article-title":"Cystatin F is secreted, but artificial modification of its C-terminus can induce its endocytic targeting","volume":"297","author":"Cappello","year":"2004","journal-title":"Exp. Cell Res."},{"key":"2021110209345942500_ref25","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1111\/j.1742-4658.2005.04594.x","article-title":"Inhibitory properties of cystatin F and its localization in U937 promonocyte cells","volume":"272","author":"Langerholc","year":"2005","journal-title":"FEBS J."},{"key":"2021110209345942500_ref26","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/sj.emboj.7601979","article-title":"Cystatin F is a cathepsin C-directed protease inhibitor regulated by proteolysis","volume":"27","author":"Hamilton","year":"2008","journal-title":"EMBO J."},{"key":"2021110209345942500_ref27","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/jnr.22567","article-title":"Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination","volume":"89","author":"Ma","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"2021110209345942500_ref28","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.mrfmmm.2011.03.018","article-title":"The Aicardi-Gouti\u00e8res syndrome. Molecular and clinical features of RNAse deficiency and micro RNA overload","volume":"717","author":"Pulliero","year":"2011","journal-title":"Mutat. Res."},{"key":"2021110209345942500_ref29","doi-asserted-by":"crossref","first-page":"34316","DOI":"10.1074\/jbc.273.51.34316","article-title":"cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism","volume":"273","author":"Lund","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021110209345942500_ref30","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1210\/en.2012-1889","article-title":"Disruption of Ror\u03b11 and cholesterol 25-hydroxylase expression attenuates phagocytosis in male Ror\u03b1sg\/sg mice","volume":"154","author":"Tuong","year":"2013","journal-title":"Endocrinology"},{"key":"2021110209345942500_ref31","doi-asserted-by":"crossref","first-page":"9620","DOI":"10.1523\/JNEUROSCI.0761-11.2011","article-title":"Interplay between LXR and Wnt\/\u03b2-catenin signaling in the negative regulation of peripheral myelin genes by oxysterols","volume":"31","author":"Makoukji","year":"2011","journal-title":"J. Neurosci."},{"key":"2021110209345942500_ref32","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1111\/j.1471-4159.2009.06009.x","article-title":"25-hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR","volume":"109","author":"Trousson","year":"2009","journal-title":"J. Neurochem."},{"key":"2021110209345942500_ref33","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms13129","article-title":"25-hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome","volume":"7","author":"Jang","year":"2016","journal-title":"Nat. Commun."},{"key":"2021110209345942500_ref34","doi-asserted-by":"crossref","first-page":"E8788","DOI":"10.1073\/pnas.1714175114","article-title":"RIPK1 mediates a disease-associated microglial response in Alzheimer's disease","volume":"114","author":"Ofengeim","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021110209345942500_ref35","doi-asserted-by":"crossref","first-page":"9714","DOI":"10.1073\/pnas.1901179116","article-title":"Targeting RIPK1 for the treatment of human diseases","volume":"116","author":"Degterev","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021110209345942500_ref36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.tcb.2019.12.009","article-title":"RIPK1 kinase-dependent death: a symphony of phosphorylation events","volume":"30","author":"Delanghe","year":"2020","journal-title":"Trends Cell Biol."},{"key":"2021110209345942500_ref37","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0092-8674(95)90070-5","article-title":"The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation","volume":"81","author":"Hsu","year":"1995","journal-title":"Cell"},{"key":"2021110209345942500_ref38","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/s41586-019-1548-x","article-title":"Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis","volume":"574","author":"Newton","year":"2019","journal-title":"Nature"},{"key":"2021110209345942500_ref39","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41419-019-1490-8","article-title":"RIPK1 can mediate apoptosis in addition to necroptosis during embryonic development","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis."},{"key":"2021110209345942500_ref40","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.tips.2016.12.005","article-title":"Complex pathologic roles of RIPK1 and RIPK3: moving beyond necroptosis","volume":"38","author":"Wegner","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"2021110209345942500_ref41","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1038\/s41467-020-15466-8","article-title":"Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation","volume":"11","author":"Laurien","year":"2020","journal-title":"Nat. Commun."},{"key":"2021110209345942500_ref42","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.4049\/jimmunol.1400590","article-title":"Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo","volume":"193","author":"Polykratis","year":"2014","journal-title":"J. Immunol."},{"key":"2021110209345942500_ref43","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.4049\/jimmunol.1400499","article-title":"Cutting edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice","volume":"192","author":"Berger","year":"2014","journal-title":"J. Immunol."},{"key":"2021110209345942500_ref44","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nm.3449","article-title":"RIPK3 as a potential therapeutic target for Gaucher's disease","volume":"20","author":"Vitner","year":"2014","journal-title":"Nat. Med."},{"key":"2021110209345942500_ref45","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1093\/hmg\/ddt190","article-title":"Missense mutation in mouse GALC mimics human gene defect and offers new insights into Krabbe disease","volume":"22","author":"Potter","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2021110209345942500_ref46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0193643","article-title":"Inhibitor of apoptosis proteins, NAIP, cIAP1 and cIAP2 expression during macrophage differentiation and M1\/M2 polarization","volume":"13","author":"Mor\u00f3n-Calvente","year":"2018","journal-title":"PLoS One"},{"key":"2021110209345942500_ref47","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.3390\/ijms18102135","article-title":"Microglia and monocytes\/macrophages polarization reveal novel therapeutic mechanism against stroke","volume":"18","author":"Kanazawa","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"2021110209345942500_ref48","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"2021110209345942500_ref49","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"2021110209345942500_ref50","first-page":"206","article-title":"Histochemishe Untersuchungen an den Globoidzellen der famili\u00e4ren infantilen diffusen Sklerose vom Typus Krabbe. (Histochemical studies on globoid bodies in Krabbe's familial infantile diffuse sclerosis, with a contribution on the differential diagnosis of central nervous system changes in Gaucher's disease.) Virchows Arch","volume":"327","author":"Diezel","year":"1955","journal-title":"Pathol. Anat. Physiol. Klin. Med."},{"key":"2021110209345942500_ref51","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0165-3806(85)90086-0","article-title":"The twitcher mouse: positive immunohistochemical staining of globoid cells with monoclonal antibody against Mac-1 antigen","volume":"352","author":"Kobayashi","year":"1985","journal-title":"Brain Res."},{"key":"2021110209345942500_ref52","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/EBC20190090","article-title":"Lyso-glycosphingolipids: presence and consequences","volume":"64","author":"Eijk","year":"2020","journal-title":"Essays Biochem."},{"key":"2021110209345942500_ref53","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1083\/jcb.149.4.943","article-title":"Inhibition of cytokinesis by a lipid metabolite, psychosine","volume":"149","author":"Kanazawa","year":"2000","journal-title":"J. Cell Biol."},{"key":"2021110209345942500_ref54","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1093\/brain\/awt215","article-title":"Inhibition of angiogenesis by \u03b2-galactosylceramidase deficiency in globoid cell leukodystrophy","volume":"136","author":"Belleri","year":"2013","journal-title":"Brain"},{"key":"2021110209345942500_ref55","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/path.4992","article-title":"Reduced cerebral vascularization in experimental neuronopathic Gaucher disease","volume":"244","author":"Smith","year":"2018","journal-title":"J. Pathol."},{"key":"2021110209345942500_ref56","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1016\/j.celrep.2015.02.051","article-title":"Activation of necroptosis in multiple sclerosis","volume":"10","author":"Ofengeim","year":"2015","journal-title":"Cell Rep."},{"key":"2021110209345942500_ref57","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1126\/science.aaf6803","article-title":"RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS","volume":"353","author":"Ito","year":"2016","journal-title":"Science"},{"key":"2021110209345942500_ref58","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/BF00293398","article-title":"Spacio-temporal progression of demyelination in twitcher mouse: with clinico-pathological correlation","volume":"88","author":"Taniike","year":"1994","journal-title":"Acta Neuropathol."},{"key":"2021110209345942500_ref59","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1101\/gad.13.19.2514","article-title":"Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis","volume":"13","author":"Lin","year":"1999","journal-title":"Genes Dev."},{"key":"2021110209345942500_ref60","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/imr.12304","article-title":"Cloaked in ubiquitin, a killer hides in plain sight: the molecular regulation of RIPK1","volume":"266","author":"Justus","year":"2015","journal-title":"Immunol. Rev."},{"key":"2021110209345942500_ref61","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/82732","article-title":"Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule","volume":"1","author":"Holler","year":"2000","journal-title":"Nat. Immunol."},{"key":"2021110209345942500_ref62","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/ni.3206","article-title":"The diverse role of RIP kinases in necroptosis and inflammation","volume":"16","author":"Rickard","year":"2015","journal-title":"Nat. Immunol."},{"key":"2021110209345942500_ref63","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.16","article-title":"Necroptosis in Niemann-Pick disease, type C1: a potential therapeutic target","volume":"7","author":"Cougnoux","year":"2016","journal-title":"Cell Death Dis."},{"key":"2021110209345942500_ref64","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00401-011-0814-2","article-title":"Axonopathy is a compounding factor in the pathogenesis of Krabbe disease","volume":"122","author":"Castelvetri","year":"2011","journal-title":"Acta Neuropathol."},{"key":"2021110209345942500_ref65","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.nbd.2019.05.011","article-title":"Dysregulated autophagy as a new aspect of the molecular pathogenesis of Krabbe disease","volume":"129","author":"Del Grosso","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"2021110209345942500_ref66","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.3390\/cells9051124","article-title":"Impairment of proteasome and autophagy underlying the pathogenesis of leukodystrophy","volume":"9","author":"Lin","year":"2020","journal-title":"Cell"},{"key":"2021110209345942500_ref67","doi-asserted-by":"crossref","first-page":"37415","DOI":"10.1074\/jbc.M110.186411","article-title":"Macroautophagy is not directly involved in the metabolism of amyloid precursor protein","volume":"285","author":"Boland","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2021110209345942500_ref68","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.4161\/auto.24919","article-title":"Altered autophagy in the mice with a deficiency of saposin A and saposin B","volume":"9","author":"Sun","year":"2013","journal-title":"Autophagy"},{"key":"2021110209345942500_ref69","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1042\/EBC20170035","article-title":"Regulation of selective autophagy: the p62\/SQSTM1 paradigm","volume":"61","author":"Lamark","year":"2017","journal-title":"Essays Biochem."},{"key":"2021110209345942500_ref70","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1093\/hmg\/ddaa277","article-title":"Brain cell type-specific endocytosis of arylsulfatase A identifies limitations of enzyme-based therapies for metachromatic leukodystrophy","volume":"29","author":"Kaminski","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"2021110209345942500_ref71","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/brain\/103.3.695","article-title":"Hereditary leucodystrophy in the mouse: the new mutant twitcher","volume":"103","author":"Duchen","year":"1980","journal-title":"Brain"},{"key":"2021110209345942500_ref72","volume-title":"Twitcher 5 Jackson; A New Remutation in the Galc Gene. MGI Direct Data Submission, J:139715","author":"Karst","year":"2008"},{"key":"2021110209345942500_ref73","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ng1095-170","article-title":"Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism","volume":"11","author":"Sango","year":"1995","journal-title":"Nat. Genet."},{"key":"2021110209345942500_ref74","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1046\/j.1471-4159.1996.66031118.x","article-title":"Molecular cloning and expression of cDNA for murine galactocerebrosidase and mutation analysis of the twitcher mouse, a model of Krabbe's disease","volume":"66","author":"Sakai","year":"1996","journal-title":"J. Neurochem."},{"key":"2021110209345942500_ref75","doi-asserted-by":"crossref","first-page":"10373","DOI":"10.1073\/pnas.0603765103","article-title":"Effective gene therapy in an authentic model of Tay-Sachs-related diseases","volume":"103","author":"Cach\u00f3n-Gonz\u00e1lez","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab159\/39741953\/ddab159.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/30\/22\/2082\/41029112\/ddab159.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/30\/22\/2082\/41029112\/ddab159.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T09:37:06Z","timestamp":1635845826000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/30\/22\/2082\/6309584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":75,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,6,25]]},"published-print":{"date-parts":[[2021,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab159","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,15]]},"published":{"date-parts":[[2021,6,25]]}}}