Accession Number:

ADA383926

Title:

Molecular Mechanisms of Dopamine Receptor Mediated Neuroprotection

Descriptive Note:

Annual rept. 15 Jul 1999-14 Jul 2000

Corporate Author:

MOUNT SINAI SCHOOL OF MEDICINE NEW YORK

Personal Author(s):

Report Date:

2000-08-01

Pagination or Media Count:

18.0

Abstract:

Exposure to specific neurotoxins can cause Parkinsons disease by killing dopaminergic neurons. These neurotoxins can cause neuronal loss by inducing apoptosis in which cell death results from sequential signalling events leading from the inducer of apoptosis to the ultimate execution of the cellular changes characteristic of this process. Evidence from our laboratory and others suggest that activation of dopamine receptors can oppose the induction of apoptosis in dopamine neurons. By integrating molecular biological, pharmacological, cell biological and physiological approaches, the points of intersection of the neurotoxin-activated pathways mediating cell death and the dopamine receptor- mediated pathways that promote survival will be investigated. The locus at which dopamine receptor activation interferes with the concatenated events mediating neurotoxin- initiated apoptosis will be determined. The sequence of events leading from activation of a specific dopamine receptor to modulation of apoptosis will be investigated. This work will identify specific molecular targets for drugs that oppose neurotoxin-mediated cell loss. The results of these studies can facilitate the development of effective, rational interventions for Parkinsons disease resulting from neurotoxin exposure. Accomplishments include establishing real-time PCR and developing and testing microarray technology for these paradigms.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE