Reversal of Mitochondrial Damage Caused by Environmental Neurotoxins
Abstract
The basic premise of this research is that the turnover of dopamine (DA) or other monoamines by monoamine oxidase (MAO) can place an oxidative stress on electron transport and respiration of mitochondria. In turn, damage to mitochondria can contribute to the progression of Parkinson's disease and to the damaging effects of environmental neurotoxins. Work conducted this past year supports the basic premise. We have shown that: (1) MAO activity suppresses both respiration and electron transport. (2) Formation of protein mixed disulfides (PrSSG) accompanies damage to mitochondria. (3) MAO inhibitors block both formation of PrSSG and mitochondrial damage. (4) MAO-A, which is the isoform of the enzyme in DA neurons, appears more active in these regards than MAO-B (glial enzyme). (5) In addition, we have developed a new and improved assay for measuring PrSSG. The new laboratory findings support the working hypothesis and help to clarify the pathophysiology of neurodegenerative mechanisms affecting DA neurons. Over the longer range, the new leads concerning thiol redox status (viz., oxidation of GSH, formation of PrSSG) can lead to improved methods to protect DA neurons from damage by environmental neurotoxins or from the ravages of Parkinson's disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA374293
Entities
People
- Gerald Cohen
Organizations
- Icahn School of Medicine at Mount Sinai