Reversibility of SCA2/ALS13: Contribution of cell types, in conditional mice

SCA2/ALS13 的可逆性：条件小鼠中细胞类型的贡献

• 批准号: 467585255
• 负责人: Professor Dr. Georg Auburger
• 金额: --
• 依托单位: Max-Planck-Institut für molekulare Genetik (MPIMG)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/467585255?language=en
• 关键词: Reversibility; SCA2; ALS13; Contribution; cell

The age-associated neurodegenerative disorders Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis (ALS13) can be prevented by depletion of ATXN2, according to data in yeast, flies and mice, so clinical trials for patients are imminent. Urgent unmet needs are the definition of the best age for intervention and of molecular progression biomarkers. As preclinical contribution and to elucidate the pathomechanism, we plan to employ an authentic mouse model where the pathogenic mutation can be deleted in cell-type-specific manner at diverse ages. Mouse tissue will be used also to identify the aberrant ATXN2 protein interactors that act as key switches between atrophy and neuroprotection. The knowledge gained will provide a basis to design additional preventive treatment approaches.

根据酵母、果蝇和小鼠的数据，与年龄相关的神经退行性疾病 2 型脊髓小脑共济失调 (SCA2) 和肌萎缩侧索硬化症 (ALS13) 可以通过消除 ATXN2 来预防，因此针对患者的临床试验迫在眉睫。迫切的未满足需求是干预最佳年龄和分子进展生物标志物的定义。作为临床前贡献并阐明病理机制，我们计划采用真实的小鼠模型，其中致病性突变可以在不同年龄以细胞类型特异性的方式被删除。小鼠组织还将用于识别异常的 ATXN2 蛋白相互作用因子，该相互作用因子充当萎缩和神经保护之间的关键开关。获得的知识将为设计额外的预防性治疗方法提供基础。