Bioenergetic Approaches and Inflammation of MPTP Toxicity

Abstract

This is a project, which has been ongoing since September of 2004. The grant initially was designed to study neuroprotective agents in an MPTP model of Parkinson's Disease (PD), as well as the pathophysiology of mitochondrial dysfunction in PD. We modified the proposal to characterize a new animal model of PD made by knocking out PINK1, a nuclear encoded kinase localized to mitochondria, and to study the effects of human doparninergic stem cells in a 6-hydroxydopamine (6-0HDA) model of PD. We also developed a new model of LRRKI induced PD in a transgenic mouse using the R1441G mutations in a BAC with full-length LRRK2. In recent studies, we studied the ability of a new technique to produce doparninergic neurons from human IPS stem cells. More recently, we revised our efforts to focus on the development of metabolomic profiling to identify biomarkers for PD. These studies have made considerable progress and we have accomplished our original goals. Outline of Research Goals: Task I: To determine the ability of pharmacologic agents to prevent MPTP neurotoxicity. Task 2: To develop a new transgenic mouse model of PD by knocking out PINK1, a protein in which mutations can cause autosomal recessive PD. Task 3: To utilize metabolomic profiling to develop biomarkers for PD. Task 4: To determine the efficacy of human dopaminergic stem cells m the 6- hydroxydopamine model of PD.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2011
Accession Number
ADA613197

Entities

People

  • M. F. Beal

Organizations

  • Cornell University

Tags

DTIC Thesaurus Topics

  • Brain
  • Cells
  • Chemistry
  • Culture Techniques
  • Detectors
  • Diseases And Disorders
  • Dysfunction
  • Liquid Chromatography
  • Mass Spectroscopy
  • Neurology
  • Neurons
  • Parkinson'S Disease
  • Proteins
  • Regenerative Medicine
  • Stem Cells
  • Toxicity

Fields of Study

  • Biology

Readers

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

Technology Areas

  • Biotechnology