The Interaction of Ataxin-1 with the RORalpha Complex in SCA1

Ataxin-1 与 SCA1 中 RORalpha 复合物的相互作用

• 批准号: 7677908
• 负责人: KRISTIN Marie GEHRKING
• 金额: $ 3.88万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677908
• 关键词: Alleles; Ataxia; Bacteria; Biochemical; Biological; Biological Assay; Complex; Development; Disease; Family; Gait abnormality; Genes; Genetic; Goals; Huntington Disease; Mediating; Modeling; Mus; Mutate; Neurodegenerative Disorders; Neurologic; Nuclear Hormone Receptors; Nuclear Inclusion; Pathogenesis; Prevention; Process; Proteins; Purkinje Cells; Research; Role; Sea; Series; Signal Transduction; Spinocerebellar Ataxias; Symptoms; Testing; Transcription Coactivator; Transgenic Mice; Type 1 Spinocerebellar Ataxia; Work; ataxin-1; base; chromatin immunoprecipitation; in vivo; mouse model; mutant; nervous system disorder; new therapeutic target; polyglutamine; promoter; research study; seal; tissue/cell culture

DESCRIPTION (provided by applicant): Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion within the SCA1-encoded protein ataxin-1. SCA1 is one of a family of nine polyglutamine diseases, including Huntington's disease. As SCA1 progresses, Purkinje cell degeneration causes cerebellar symptoms, including gait abnormalities and loss of coordination. Previous work has shown that proper cerebellar development is coordinated by RORalpha, a nuclear hormone receptor. Furthermore, RORalpha and ataxin-1 interact in vivo and share a common set of signaling targets. Purkinje cell RORalpha levels are decreased in SCA1 mice, but can be rescued by turning off ataxin-1 expression, suggesting a role for RORalpha in the prevention of SCA1 pathogenesis. This goal of this research is to determine whether loss of RORalpha exacerbates the degeneration associated with SCA1, providing new therapeutic targets for this family of neurodegenerative diseases.

描述（由申请人提供）：