"Genes and poisons involved in Parkinson's disease"
Prof. Jean-Christophe Rochet
Department of Medicinal Chemistry and Molecular Pharmacology
Purdue University
Abstract
Parkinson's disease (PD) is a debilitating neurodegenerative disorder that results from a progressive loss of neurons in the midbrain.
The affected neurons are responsible for producing dopamine, a critical neurotransmitter that modulates movement and other aspects of human behavior.
The postmortem brains of Parkinson's patients are characterized by damage from oxidizing 'poisons' and characteristic deposits named Lewy bodies, which consist of fibrils formed from the protein alpha-synuclein.
Mutations in the gene encoding alpha-synuclein are involved in early-onset, inherited forms of PD.
The disease-linked mutants have a greater tendency to form aggregates than the wild-type protein, suggesting that alpha-synuclein aggregation plays a role in neurodegeneration.
In addition, various environmental poisons (e.g. pesticides, metals) have been shown to produce a PD-like phenotype in cell culture and animal models.
A goal of our research is to understand mechanisms of cell death in PD, with an emphasis on how genes and the environment interact to cause the selective death of dopamine neurons in patients.
Data from these studies provide insight into the role of alpha-synuclein and environmental toxins in PD, and they suggest strategies for therapeutic development.