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

Abstract

Purpose: 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 determined splicing products in the brain and blood of experimental MPTP models of PD. The overall goal was 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 also had lRB permission (for only 9 months) to study splicing factors in the blood of 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 have demonstrated that AChE variant R is upregulated in the striatum and blood after MPTP. No patients were enrolled for th ehuman blood study and that study is closedOverall we have published four articles and have three in preparation.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2008
Accession Number
ADA488486

Entities

People

  • Gloria E. Meredith

Organizations

  • Rosalind Franklin University of Medicine and Science

Tags

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Blood-Brain Barrier
  • Brain
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Diseases And Disorders
  • Genetics
  • Neurodegeneration
  • Neuroglia
  • Neurons
  • Neurosciences
  • Parkinson'S Disease
  • Proteins

Fields of Study

  • Biology
  • Medicine

Readers

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  • Neurodegenerative Parkinson's Disease and Rickettsial Disease handbook, including the data level of dopamine, BC, neurons, and PD.