Is Protein Misfolding and Aggregation a Common Disease Mechanism?

Abstract

ABSTRACT It has been known for several decades that protein aggregation is a hallmark of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease). It was assumed that these aggregations, which are closely associated with the lesions or plaques characteristic of these diseases, formed as a byproduct by the neurodegenerative disease process. This view of neurodegenerative diseases has changed dramatically over the last few years. It is now clear that protein aggregates are seen in the early stages of pathogenesis, suggesting that they are not the result of cellular damage. Furthermore, evidence that these insoluble complexes are cytotoxic and trigger apoptosis suggest that protein aggregation plays a seminal role in the etiology of neurodegenerative diseases. New evidence extends these finding further by demonstrating that insoluble protein aggregates of non-disease related proteins are toxic to cells and that the ubiquitin, w...