AGENT FOR PREVENTING OR TREATING SPINOCEREBELLAR ATAXIA

摘要

To provide a compound which enables treatment or prevention of spinocerebellar ataxia, analyses were carried out based on a screening using a spinocerebellar ataxia type 1 (SCA1) fly model and on the like. As a result, the following proteins ameliorating the pathology of spinocerebellar ataxia were identified: RPA1, PNKP, XRCC3, XRCC4, CCNH, POLE, POLH, and PERI. On the other hand, the following proteins aggravating the pathology were identified: CHK1, LIG3, FEN1, LIG1, ERCC5, XAB2, ERCC2, DMC1, RECQL5, MUS81, EME1, SPO11, and BLM. In addition, it has been revealed that ATXN1, which is a cause of SCA1, binds to RPA1, BRCA1, and BRCA2, and suppresses the activities of these proteins, so that the above-described pathology is caused.

主权项

1. An agent for preventing or treating spinocerebellar ataxia, comprising, as an active ingredient, at least one of the following (a) to (d):
(a) at least one protein selected from the group consisting of RPA1, BRCA1, BRCA2, PNKP, XRCC3, XRCC4, CCNH, POLE, POLH, and PER1 or a nucleic acid encoding the protein; (b) a compound which enhances expression or activity of at least one protein selected from the group consisting of RPA1, BRCA1, BRCA2, PNKP, XRCC3, XRCC4, CCNH, POLE, POLH, and PER1; (c) a compound which inhibits binding between ATXN1 and at least one protein selected from the group consisting of RPA1, BRCA1, and BRCA2; and (d) a compound which suppresses expression or activity of at least one protein selected from the group consisting of CHK1, LIG3, FEN1, LIG1, ERCC5, XAB2, ERCC2, DMC1, RECQL5, MUS81, EME1, SPO11, and BLM.