Aberrant protein structure and diseases of the brain.

Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein aggregates are pathological hallmarks of several neurodegenerative disorders and it has been hotly debated whether these aberrant protein structures merely occur as a consequence of disease or actually participate in a pathogenic cascade which culminates in neural dysfunction and death. Here, we review the role of aberrant protein structure in the two most common neurodegenerative disorders: Alzheimer's disease and Parkinson's disease and in two rare familial dementias, familial British dementia and familial Danish dementia. We also discuss possible mechanisms by which aberrant protein structures may mediate disease and the therapeutic opportunities this knowledge offers.