Bioenergetic Approaches and Inflammation of MPTP Toxicity
Abstract
This project was to develop novel therapies for Parkinson's Disease (PD), to test the effects of human dopaminergic stem cells, and to utilize metabolomic profiling to develop biomarkers for PD. We also developed a new transgenic mouse model of PD by knocking out the gene PINKI. Utilizing microdialysis we showed that PINK I deficient mice have impaired dopamine release. We demonstrated that rolipram, mitochondrial targeted antioxidant peptides, celastrol and promethazine were neuroprotective against MPTP toxicity. We showed that novel forms of Coenzyme Q, exert neuroprotective effects. We demonstrated that MMP3 knockout mice were protected against MPTP toxicity. Utilizing microdialysis, we showed that PINK I deficient mice have impaired dopamine release. We showed that human dopaminergic stem cells reverse deficits in the 6-hydroxy-dopamine model of PD. We carried out studies using metabolomic profiling to develop biomarkers for PD. We utilized metabolomic profiling with high performance liquid chromatography coupled to electrochemical coulometric array detection. In these studies, we were able to completely separate unmedicated PD subjects from controls, We subsequently were able to clearly separate PD patients with the LRRK2 mutations from idiopathic PD and controls, Similarly, we could separate gene positive patients from both controls and LRRK2 mutation negative patients. Lastly, we studied a number of agents which produced significant neuroprotective effects against MPTP toxicity and which therefore might be useful in human clinical trials to treat PD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2009
- Accession Number
- ADA508622
Entities
People
- M. F. Beal
Organizations
- Cornell University