Reversal of Mitochondrial Damage Caused by Environmental Neurotoxins
Annual rept. 1 Sep 1998-1 Sep 1999
MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
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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 Parkinsons 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 Parkinsons disease.