AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease
نویسندگان
چکیده
منابع مشابه
Systemic AAV9 gene therapy improves the lifespan of mice with Niemann-Pick disease, type C1.
Niemann-Pick disease, type C1 (NPC1) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of NPC1 disease (Npc1-/-) displays a rapidly progressing form of NPC1 disease which is characterized by weight loss, ataxia, increased cholesterol storage, loss of cerebellar Purkinje neurons and early l...
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Pathways regulating neuronal vulnerability are poorly understood, yet are central to identifying therapeutic targets for degenerative neurological diseases. Here, we characterize mechanisms underlying neurodegeneration in Niemann-Pick type C (NPC) disease, a lysosomal storage disorder characterized by impaired cholesterol trafficking. To date, the relative contributions of neuronal and glial de...
متن کاملA novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations.
We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease: a single nucleotide change (A to G at cDNA bp 3163) that results in an aspartate to glycine change at position 1005 (D1005G). This change is in the cysteine-rich luminal loop of the NPC1 protein and is highly similar to commonly occurring human mutations. Genetic an...
متن کاملMouse behavioral mutants have neuroimaging abnormalities.
Impaired cognitive, memory, or motor performance is a distinguishing characteristic of neurological diseases. Although these symptoms are frequently the most evident in human patients, additional markers of disease are critical for proper diagnosis and staging. Noninvasive neuroimaging methods have become essential in this capacity and provide means of evaluating disease and tracking progressio...
متن کاملTemporal and cell-specific deletion establishes that neuronal Npc1 deficiency is sufficient to mediate neurodegeneration.
Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in the NPC1 or NPC2 genes. Loss of function mutations in either gene disrupt intracellular lipid trafficking and lead to a clinically heterogeneous phenotype that invariably includes neurological dysfunction and early death. The mechanism by which impaired lipid transport leads to neurodeg...
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ژورنال
عنوان ژورنال: Journal of Lipid Research
سال: 2017
ISSN: 0022-2275
DOI: 10.1194/jlr.m071274