Neurodegenerative diseases are caused by progressive degeneration of specific neurons. To overcome neurodegenerative diseases, the exploitation of preventive drugs is strongly expected, since impaired neurons are not regenerated by drugs. Spinocerebellar ataxia (SCA) is a group of dominantly-inherited neurodegenerative diseases. SCA is classified into SCA1-47 by the variance of causal genes. Since SCA patients are commonly characterized by cerebellar ataxia and atrophy of cerebellum, it is possible that there are common pathogenic mechanisms in SCAs. However, we can not find any shared functions among SCA-causing proteins. We have explored the molecular pathogenesis of several SCA-causing proteins. Especially, we have constructed in vitro SCA model to express these mutant proteins in primary cultured cerebellar Purkinje cells (PCs), which are characterized highly-branched dendrites and are important for cerebellar functions. Several SCA-causing mutant proteins commonly impair dendritic development of PCs. We assume that this phenomenon is one of the common phenotypes of SCA in vitro. This SCA model would be useful for the efficient exploration of novel preventive drugs against various types of SCAs.

To: 要旨(抄録)