The Identification of Splice Variants as Molecular Markers in Parkinson's Disease

Abstract

Alternative splicing is responsible for producing several products from a single transcript and can cause pathogenic changes in RNA in neurodegenerative disease. This proposal tests the hypothesis that regulation of normal splicing is disrupted in Parkinson's disease (PD). Scope: Experiments are designed to determine splicing products in the brain and blood of experimental MPTP models of PD and the blood of newly diagnosed PD patients, who are not yet on dopamine therapy. The overall goal is to use splice variants as biomarkers to identify individuals at risk for PD. To date, we have identified and quantified alternatively spliced transcripts for several candidate genes in MPTP models of PD. We have also obtained IRB permission to study splicing factors in the blood of newly diagnosed PD patients. Major Findings: Mice treated acutely and chronically with MPTP show a shift in the ratio of FosB, RGS9, AChe and Ania6 splice variants in the striatum and blood. Gene expression (in situ hybridization) studies are in progress to localize the variants in the brain. Progress in the second year includes 3 abstracts, one published article, a second article submitted and an article in preparation.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2007
Accession Number
ADA476088

Entities

People

  • Gloria E. Meredith

Organizations

  • Rosalind Franklin University of Medicine and Science

Tags

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Alzheimer Disease
  • Brain
  • Cells
  • Chemistry
  • Dementia
  • Diseases And Disorders
  • Gene Expression
  • Health Services
  • Institutional Review Board
  • Lymphocytes
  • Neurodegeneration
  • Neurodegenerative Diseases
  • Neurons
  • Neurosciences
  • Parkinson'S Disease
  • Proteins

Fields of Study

  • Biology

Readers

  • Infectious Disease/Epidemiology
  • Molecular Biology and Genetics
  • Neurodegenerative Parkinson's Disease and Rickettsial Disease handbook, including the data level of dopamine, BC, neurons, and PD.