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• W2065519995 abstract "Niemann-Pick type C (NPC) disease is a genetic disorder associated with intracellular cholesterol accumulation in the brain and other organs, and neurodegeneration is generally believed to be the fatal cause of the disease. In view of the emerging role of matrix metalloproteinase-12 (MMP-12) in neuronal injury, we investigated its expression and potential roles in axonal degeneration in Npc1-/- mouse brain. Microarray and quantitative real-time reversed transcription PCR analysis indicated a marked increase in MMP-12 mRNA levels in cerebellum of 3 week-old Npc1-/- mice, as compared to wild-type littermates. Western blots showed that the ratio of mature MMP-12 over pro-MMP-12 was significantly increased in cerebellum of Npc1-/-, as compared to wild-type mice. Immunohistochemical studies confirmed that MMP-12 expression was increased, especially in the cell bodies of Purkinje neurons in Npc1-/- mice. Neuritic growth was significantly reduced by Npc1 siRNA knockdown in nerve growth factor-differentiated PC-12 cells, and this effect was completely reversed by treatment with an MMP-12 specific inhibitor. Furthermore, in vivo experiments showed that chronic treatment with the MMP-12 inhibitor ameliorated Npc1 deficiency-induced axonal pathology in the striatum. Our results indicate that abnormal neuronal expression of MMP-12 may contribute to axonal degeneration in NPC disease, thus providing a potential novel target for treatment." @default.
• W2065519995 created "2016-06-24" @default.
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• W2065519995 date "2015-07-01" @default.
• W2065519995 modified "2023-10-05" @default.
• W2065519995 title "Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency-induced axonal degeneration" @default.
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• W2065519995 doi "https://doi.org/10.1016/j.expneurol.2015.04.004" @default.
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