Is there a cause-and-effect relationship between alpha-synuclein fibrillization and Parkinson's disease?

The first gene to he linked to Parkinson's disease encodes the neuronal pro tein alpha-synuclein. Recent mouse and Drosophila models of Parkinson's dis ease support a central role for the process of alpha-synuclein fibrillizati on in pathogenesis. However, some evidence indicates that the fibril itself may not be the pathogenic species. Our own biophysical studies suggest tha t a structured fibrillization intermediate or an alternatively assembled ol igomer may be responsible for neuronal death. This speculation can now be e xperimentally tested in the animal models. Such experiments will have impli cations for the development of new therapies for Parkinson's disease and re lated neurodegenerative diseases.