|Mitochondria: Another Dimension in Protein Misfolding
A growing body of evidence indicates that mitochondrial abnormalities play an important role in the development of neurodegenerative diseases. In addition, mitochondrial abnormalities appear to be a central target in the development and maturation of neurodegeneration, specifically, Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). Recent work from our laboratories demonstrated that mitochondrial abnormality indeed appears to be a primary target for brain damage as a surrogate for amyloid deposition, as is seen in human AD and transgenic mouse models of AD.
Recent findings by Vijayvergiya and coworkers demonstrated that a mutant form of superoxide dismutase 1 forms aggregates in the brain mitochondrial matrix of amyotrophic lateral sclerosis mice. Because SOD1 is largely a cytosolic protein, it is shuttled to the mitochondria. A portion of SOD1 is localized in the mitochondria of patients with familial amyotrophic lateral sclerosis (FALS) as well as in a transgenic mouse...