Alpha-synuclein Involvement in Transmitter Release

Ottavio Arancio, M.D., Ph.D.
The Nathan S. Kline Institute for Psychiatric Research, New York


Dr. Ottavio Arancio is attempting to advance our understanding of the effects of both normal and mutated alpha-synuclein, a protein found in neurons. A mutated version of the alpha synuclein gene has been associated with several of the familial parkinsonisms already described and is also known to be a major component of Lewy bodies, a hallmark of classic PD that, when found on autopsy, confirms the patient's diagnosis. He and his colleagues at the Nathan S. Kline Institute/New York University (Orangeburg, New York) have cultured hippocampal (a brain area) neurons from laboratory rats on which they plan to test their theories of the effects of this abundant neuronal protein.

Progress Report (as of 3/2003)

The term synucleinopathies was coined a few years ago to denote neurologic disorders in which the protein alpha-synuclein is involved. Then it was learned that the hallmark of PD, the Lewy body (LB), is composed partly of @-synuclein, and that mutations of this protein are seen in the brains of certain familial parkinsonism subjects. These findings have resulted in literally hundreds of @-synuclein studies, and one has been used by Dr. Ottavio Arancio and his team at the Nathan S. Kline Institute (New York). They have shown that when this protein malfunctions, it not only aggregates in LBs, but increases the frequency of dopamine release, resulting in excitotoxicity that, in turn, damages neurons. Additional efforts are aimed at determining which enzymes may be responsible for the aggregations in PD brains. Dr. Arancio presented these data at the Society for Neurosciences meeting during the course of his grant.