Protection by Purines in Toxin Models of Parkinson's Disease
Abstract
In Year 3 of the project progress has been made toward our original Specific Aims (SAs) and broader central goal of elucidating the neuroprotective potential and mechanisms of purines implicated in the neurodegeneration of Parkinson s disease (PD). Published findings during Year 3 included our demonstrations that lowering urate in vivo using allopurinol could exacerbate neurotoxicity at the level of striatal dopamine (SA2); and that inosine a urate precursor could be protective in its own right against dopaminergic cell death in a cell culture model of PD(SA3). We also published methodological progress developing a new generation of more refined genetic probes of urate neurobiology. Recently we have obtained preliminary data identifying the Nrf2 antioxidant response pathway as an astrocytic mediator of urate s neuroprotective effects.Together our findings strengthen the rationale for pursuing purine targets as candidate neuroprotective strategies for PD, and have epidemiological and military, as well as translational significance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2014
- Accession Number
- ADA608811
Entities
People
- Michael A Schwarzschild
Organizations
- Massachusetts General Hospital