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- W2075950657 abstract "Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder, which is caused by missense mutations of PRKCG gene encoding γ type protein kinase C (γPKC). To elucidate the pathophysiology of SCA14, we have analyzed the character of mutant γPKC causing SCA14, expressed in cultured cells.We found that most of mutant γPKCs were susceptible to cytoplasmic aggregation, suggesting that this aggregate-prone is involved in the etiology of SCA14. When expressed in cultured Purkinje cells, mutant γPKC inhibited the development of dendrites in a manner independent of its aggregate-prone, suggesting that other mechanism is implicated in the pathogenesis of SCA14. FRAP (fluorescence recovery after photobleaching) analysis demonstrated that mobility of mutant γPKC was slower than that of wild type in Purkinje cells. Furthermore, translocation of mutant PKC was attenuated when the cells was treated with high potassium solution. These results suggest that mutant γPKC forms oligomers in Purkinje cells. In addition, enzymological studies revealed that most of mutant γPKC had higher basal activity than wild one. However, the imaging analysis of γPKC demonstrated that mutations slowed the translocation of γPKC, which may explain the low accessibility of mutant γPKC to the plasma membrane.We propose that variety of mutant γPKC characters integrally and complicatedly participate in the pathophysiology of SCA 14." @default.
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- W2075950657 date "2011-09-01" @default.
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- W2075950657 title "Molecular pathophysiology of neurodegenerative disease caused by γPKC mutations" @default.
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- W2075950657 doi "https://doi.org/10.3109/15622975.2011.598688" @default.
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