Protein aggregation in Huntington's and Parkinson's disease: implications for therapy

The accumulation of highly insoluble intracellular protein aggregates in neuronal inclusions is a hallmark of Huntington's disease (HD) and Parkinson's disease (PD) as well as several other late-onset neurodegenerative disorders. The aggregates formed in vitro and in vivo generally have a fibrillar morphology, consist of individual beta-strands and are resistant to proteolytic degradation. Although the causal relationship between aggregate formation and disease remains to be proven, the gradual deposition of mutant protein in neurons is consistent with the late-onset and progressive nature of symptoms. Recently, circumstantial evidence from mouse and Drosophila model systems suggests that abnormal protein folding and aggregation play a key role in the pathogenesis of both HD and PD. Therefore, a detailed understanding of the molecular mechanisms of protein aggregation and its effects on neuronal cell death could open new opportunities for therapy.