Cell Signaling and Neurodegeneration

描述（由申请方提供）：脊髓小脑共济失调1型（SCA 1）是一种无法治疗的致死性常染色体显性遗传神经退行性疾病，由SCA 1编码的蛋白ATXN 1内谷氨酰胺重复序列扩增引起。先前的工作表明ATXN 1通过丝氨酸残基776的磷酸化修饰，并且这种磷酸化对于突变体ATXN 1引起疾病至关重要。最近来自母项目的证据表明PKA介导丝氨酸776的磷酸化。本申请是对通知号（NOT-OD-09-058）“NIH宣布恢复法案资金用于竞争性修订申请的可用性”的回应，要求进行高通量筛选并优化丝氨酸776的PKA介导磷酸化抑制剂的先导化合物。

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.