Mitochondrial Dysregulation in Skeletal Muscle from Patients Diagnosed with Alzheimer’s Disease and Sporadic Inclusion Body Myositis

• 作者: Elika Shabrokh John Kavanaugh Josh Pittman Madlyn Frisard Matt Hulver Ryan McMillan
• 来源期刊: 分子和综合生理学期刊(英文)
• 学科: 医学
• 关键词: MITOCHONDRIAL Dynamics Autophagy MITOCHONDRIAL BIOGENESIS Amyloid Beta Precursor PROTEIN 5’-AMP-Activated PROTEIN Kinase
• 年，卷（期）: 2014,（2）
• 页码范围: 11-19
• 页数: 9页
• 分类号: R73

摘要

Mitochondrial dysfunction is implicated in Alzheimer’s disease (AD) and disruption of mitochondrial dynamic pathways has been documented in brains from patients diagnosed with AD;although it is unclear whether other tissues are also affected. Much less is known about the mitochondria in patients diagnosed with sporadic Inclusion Body Myositis (sIBM). The current study examined mitochondrial biology in skeletal muscle from AD and sIBM patients compared to healthy, elderly individuals. Skeletal muscle samples were obtained from the National Disease Research Interchange and mRNA, protein content, and enzyme activity was used to assess mitochondrial parameters. Patients diagnosed with AD or sIBM demonstrated reduced mitofusin 2 and optic atrophy protein 1 protein. AD patients also displayed increased mRNA of superoxide dismutase 2, catalase, and uncoupling protein 3. Amyloid b precursor protein mRNA was higher in sIBM patients only compared to both AD patients and elderly individuals. Both total and phosphorylated AMPK protein content, an upstream regulator of mitochondrial dynamics and biogenesis, were also reduced in sIBM patients. The current study demonstrates a disruption in signaling pathways regulating mitochondrial dynamics in both AD and sIBM patients, although the underlying causes may differ.