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Abstract

Grant Number:	5P50NS038372-05
Project Title:	MGH/MIT PARKINSONS DISEASE RESEARCH CENTER

PI Information:	Name	Email	Title
	YOUNG, ANNE B.	young@helix.mgh.harvard.edu	PROFESSOR

Abstract: Submitted in response to RFA NS-98-001 this center will study how aberrant trafficking of alpha-synuclein, which may involve the two novel proteins (parkin and torsinA), leads to the death of dopamine neurons in Parkinson's disease. We will also study the nature of the basal ganglia dysfunction caused by parkinsonism and we will use the techniques so developed to validate our models of molecular mechanisms. Four projects and two cores will be involved. The first project, under Dr. Bradley Hyman, will determine the role of alpha-synuclein in Lewy body formation using transgenic animals and confocal microscopy. The second, under Dr. Xandra Breakefield, will use molecular biological techniques to determine the degree to which different alleles of the genes for alpha-synuclein, parkin, torsinA, which is mutated in early onset torsion dystonia, and that for Rapid Onset Dystonia Parkinsonism contribute to the susceptibility to Parkinson's disease. The third project, under Dr. John Penney, will determine if the most vulnerable dopamine neurons are the ones that bear the highest burden of these potentially pathogenic molecules using double-label in situ hybridization and antisense RNA techniques. The fourth project, under Dr. Ann Graybiel, will focus on determining the neural systems consequences of parkinsonism and the alpha- synuclein and dystonia mutations in experimental animals using tetrode recordings. The projects are highly integrated, each interacting extensively with all the others to contribute to the overall program. The center will be supported by an administrative core and a vital, training and clinical core that will provide a superb training ground for the next generation of parkinson's disease researchers. Finally, the two institutions involved ensure that the center will exist in a highly supportive environment.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
Parkinson's disease, alpha synuclein, pathologic process

Institution:	MASSACHUSETTS GENERAL HOSPITAL
	Partners Research Management
	BOSTON, MA 02199
Fiscal Year:	2002
Department:
Project Start:	30-SEP-1998
Project End:	31-JUL-2004
ICD:	NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG:	ZNS1

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