Mechanisms of Programmed Cell Dealth in a Model of Parkinson’s Disease



Allen S. Mandir, M.D., Ph.D.
The Johns Hopkins University, School of Medicine, Maryland


Dr. Allen D. Mandir of Johns Hopkins University (Baltimore) will compare the reactions to a neurotoxin that causes parkinsonism (MPTP) in two types of mice; one carrying the gene for PARP (an enzyme thought to be involved in DNA repair), the other having had that gene deleted or "knocked out." This basic science work is designed to help in the understanding of PD-caused neuronal degeneration, more specifically, why only certain neurons die in a "selective" manner. Dr. Mandir hopes to elaborate on the roles (and interactions) of genetic susceptibility, the environment, and stresses produced within patients' bodies.

Progress Report (as of 3/2003)

A neuroscience group at Johns Hopkins (Baltimore) has been trying to solve the mysteries of apoptosis or programed cell death in parkinsonism. Dr. Allen S. Mandir and his colleagues published their early data showing that MPTP toxicity causes DNA damage that in turn signals the activation of a protein (p53). While p53 inhibits the replication of damaged cells (good), it also activates other proteins that induce apoptosis (bad). They then found that a nuclear enzyme (PARP), also activated by MPTP, serves to stabilize p53, thus attenuating apoptosis. Now if they could only connect this to classic Parkinson’s Disease, their knowledge could help human patients.

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