PINK1 signaling and synaptic mitochondria integrity in AD

AD 中的 PINK1 信号传导和突触线粒体完整性

• 批准号: 10091121
• 负责人: SHI FANG YAN
• 金额: $ 22.73万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091121
• 关键词: PINK1; signaling; synaptic; mitochondria; integrity

Summary Mitochondrial dysfunction is the early pathological feature of Alzheimer’s disease (AD)-affected brain. Memory impairment in AD is a manifestation of brain pathologies such as accumulation of amyloid-β peptide (Aβ) and mitochondrial damage. Damaged mitochondria are progressively accumulated in brain over the lifetime of AD- affected neurons, which is likely attributable to inadequate clearance capacity in removing increased numbers of defective mitochondria from nerve cells. Therefore, increased or decreased levels of defective or healthy mitochondria in AD brains disturb the homeostatic balance between healthy and dysfunctional mitochondria, leading to mitochondrial pathology and contributing to cognitive dysfunction. The underlying pathogenic mechanisms and effective disease modifying therapies for AD remain elusive. PTEN-induced putative kinase 1 (PINK1) is important for maintaining mitochondrial integrity and quality control. So far, the role of PINK1 in mitochondrial pathology and cognitive dysfunction in AD remains unexplored. We hypothesize that the impairment of PINK1 function in AD underlies mitochondrial degeneration, leading to cognitive decline. Utilizing gene delivery of PINK1 technology, novel transgenic PINK1/AD models, we will elucidate PINK1- dependent mechanisms underlying Aβ-mediated mitochondrial alterations. The completion of this project will open up a new avenue for the treatment of AD by targeting PINK1 to maintain mitochondrial integrity.

总结

项目成果

Mitochondrial permeability transition pore: a potential drug target for neurodegeneration.

• DOI: 10.1016/j.drudis.2018.08.001
• 发表时间: 2018-12
• 期刊: Drug discovery today
• 影响因子: 7.4
• 作者: Kalani K;Yan SF;Yan SS
• 通讯作者: Yan SS