TITLE:
Mitochondrial Dysregulation in Skeletal Muscle from Patients Diagnosed with Alzheimer’s Disease and Sporadic Inclusion Body Myositis
AUTHORS:
Elika Shabrokh, John Kavanaugh, Ryan McMillan, Josh Pittman, Matt Hulver, Madlyn Frisard
KEYWORDS:
Mitochondrial Dynamics, Autophagy, Mitochondrial Biogenesis, Amyloid Beta Precursor Protein, 5’-AMP-Activated Protein Kinase
JOURNAL NAME:
Open Journal of Molecular and Integrative Physiology,
Vol.4 No.2,
May
16,
2014
ABSTRACT: 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.