title: Deletion of mitochondrial anchoring protects dysmyelinating shiverer: implications for progressive MS.
abstract: The demyelinating disease multiple sclerosis (MS) has an early inflammatory phase followed by an incurable progressive phase with subdued inflammation and poorly understood neurodegenerative mechanism. In this study, we identified various parallelisms between progressive MS and the dysmyelinating mouse model Shiverer and then genetically deleted a major neuron-specific mitochondrial anchoring protein Syntaphilin (SNPH) from the mouse. Prevailing evidence suggests that deletion of SNPH is harmful in demyelination. Surprisingly, SNPH deletion produces striking benefits in the Shiverer by prolonging survival, reducing cerebellar damage, suppressing oxidative stress, and improving mitochondrial health. In contrast, SNPH deletion does not benefit clinical symptoms in experimental autoimmune encephalomyelitis (EAE), a model for early-phase MS. We propose that deleting mitochondrial anchoring is a novel, specific treatment for progressive MS.
authors.affiliation: Department of Neuroscience.
authors.forename: Dinesh C
authors.initials: DC
authors.lastname: Joshi
authors.affiliation: Department of Neuroscience.
authors.forename: Chuan-Li
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience.
authors.forename: Tien-Min
authors.initials: TM
authors.lastname: Lin
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: Anchal
authors.initials: A
authors.lastname: Gusain
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, and.
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Harris
authors.affiliation: Department of Neuroscience.
authors.forename: Esther
authors.initials: E
authors.lastname: Tree
authors.affiliation: Department of Neuroscience.
authors.forename: Yewin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Neuroscience.
authors.forename: Connie
authors.initials: C
authors.lastname: Wu
authors.affiliation: Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Zu-Hang
authors.initials: ZH
authors.lastname: Sheng
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Dempsey
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, and.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fabry
authors.affiliation: Department of Neuroscience, schiu1@wisc.edu.
authors.forename: Shing Yan
authors.identifier: http://orcid.org/0000-0002-6532-8029
authors.initials: SY
authors.lastname: Chiu
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D066128:Gray Matter / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000628:therapy; D009419:Nerve Tissue Proteins; D018384:Oxidative Stress / Q000235:genetics; D016019:Survival Analysis; D066127:White Matter / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C527531:Snph protein, mouse
keywords: axonal degeneration; mitochondria; multiple sclerosis; oxidative stress; syntaphilin
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