Cell Signaling and Neurodegeneration

描述（由申请人提供）：脊髓小脑性共济失调1型（SCA1）是一种无法治疗的致命常染色体显性神经退行性疾病，由SCA1编码蛋白ATXN1内谷氨酰胺重复扩增引起。先前的研究表明，ATXN1通过丝氨酸残基776的磷酸化修饰，这种磷酸化对于突变ATXN1致病至关重要。最近来自母体项目的证据表明，PKA介导丝氨酸776的磷酸化。根据通知号（no - od -09-058），“NIH宣布为竞争性修订申请提供恢复法案资金”，该申请要求对pka介导的丝氨酸776磷酸化抑制剂进行高通量筛选和先导化合物优化。

DESCRIPTION (provided by applicant): Spinocerebellar ataxia type 1 (SCA1) is an untreatable fatal autosomal dominant neurodegenerative disorder caused by the expansion of a glutamine repeat within the SCA1-encoded protein ATXN1. Previous work showed that ATXN1 is modified by phosphorylation at serine residue 776 and this phosphorylation is critical for mutant ATXN1 to cause disease. Recent evidence form the parent project indicates that PKA mediates the phosphorylation of serine 776. This application, in response to Notice Number (NOT-OD-09-058), "NIH Announces the Availability of Recovery Act Funds for Competitive Revisions Applications" is a request to undertake a high-throughput screen and lead compound optimization for inhibitors of PKA-mediated phosphorylation of serine 776.