Accession Number:

ADA434051

Title:

Oxidative Damage in Parkinson's Disease

Descriptive Note:

Final rept. 1 Jan 2003-31 Dec 2004

Corporate Author:

MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s):

Report Date:

2005-01-01

Pagination or Media Count:

86.0

Abstract:

The overall goal of the proposal was to provide a detailed assessment of the role of oxidative damage in Parkinsons disease PD and the MPTP model of PD. During our one year addendum, we carried out studies which showed the anti-inflammatory agent minocycline exacerbated MPTP neurotoxicity. The anti-inflammatory compound rolipram produced dose-dependent neuroprotective effects against MPTP. Administration of the iron chelator clioquinol was neuroprotective against MPTP and this was associated with reduced oxidative stress. Systemic administration of a broad spectrum caspase inhibitor produced neuroprotection against MPTP toxicity as assessed by loss of both dopamingeric neurons and dopamine levels. We demonstrated for the first time that MMP-9 is increased after administration of MPTP. MMP-9 may be activated by oxidative stress. We found that a broad spectrum inhibitor MMP inhibitor protected against dopamine depletion and loss of tyrosine hydroxylase neurons. We carried out studies showing that a deficiency of DJ-1, which is linked to autosomal recessive PD, results in cells being more vulnerable to oxidative damage. We found that novel azulenyl nitrone was markedly neuroprotective against MPTP and prevented increases in malondialdehyde in vivo. These studies, therefore, have provided further evidence for oxidative damage in the pathogenesis of PD.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE