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>To: [log in to unmask] >From: [log in to unmask] (Steven E. Mayer) >Subject: Mitochondria in Parkinsonism & Emory U. > > >I may be able to shed some light on the role of mitochondria in brain aerobic (oxygen-using) metabolism. As far as the Emory PD surgery group is concerned, it has achieved a great deal of success with pallidotomy to treat PD with minimum serious after-effects. The waiting list for surgery is said to be 2 1/2 years and follows very carefull evaluation. I am an ex-Emory professor (in pharmacology and brain chemistry). I wait along with all the others. Mitochondria are normal constituents of almost all types of organisms and cellls (except prokaryocytes - bacteria). Mitochondria are essential for the synthesis of energy-rich compounds, that are used by cells to contract (muscle), transport (kidney), synthesize neurotransmitters (e.g. L-dopamine), generate electrical impulses (nerve cells). Brain mitochondria are near the top in concentration compared to other cells. They are absolutely necessary for life. A few minutes of deprivation of oxygen and glucose in the blood perfusing the brain is fatal for most nerve cells when they are deprived of the fuel the mitochondrial engine converts into the energy needed for nerves to conduct electric current, to synthesize neurotransmitters, maintain the normal salt-water balance of the brain, etc. I have had experience doing research on brain mitochondria, in fact, at Emory, where I was on the medical school faculty from 1957-1969 (I am not a neurosurgeon). My subsequent research at the University of California, San Diego (1969-1985) and Vanderbilt University Medical center has involved studies of toxins, such as mercury and lead on brain cell mitochondria. Your E-mail message suggesred that your mother is struggling with mitochondria (instead of PD?). Her brain mitochondria may be damaged, which in turn may produce (some) PD symptoms. PD is unlikely to be a disease primary to mitochondria, but the oxidative capacity of nigrostriatal neuronal mitochondria might be the site of an environmental toxin (MPTP-like??) or a defect in the synthesis or utilization by brain cells of a substance(s) the cells synthesize: NADH (Nicotinamide adenine dinuceotide, reduced) NADH is absolutely essential for the synthesis of high-energy compounds by brain mitochondria by participating in electron transport coupled to high-energyphosphate bond formation. If this is compromisedn manner, the capacity of dopamine-producing cells in selected areas of the brain will be compromised, a dopamine deficiency results leading to parkinsonism. This is, as yet, a big hypothesis to swallow, but it makes sense. SEE J.R. NEWBROUGH, 12/24/9 message [log in to unmask] This does not instantly make NADH the miracle-drug for PD..Based in part on my own work on brain high-ebergy compounds, I am skeptical that NADH would make a useful drug. A problem would be how to get the NADH to its putative site(s) of action which may be located at possibly inaccessible sites within the nerve cells. I have frequently noted complaints from readers that a new candidate drug has not been tested, depriving possible benefits to ill and loved patients. Unfortunately, thousands of promising therapeutic agents never make it from the cell culture to the patient, because of the tactical problem(s) encountered in trying to get the drug to the right place at the right time in effective, but non-toxic concentrations. A challenge to us biochemists and pharmacologists, indeed. This is by no means a complete review, nor is it very literate. I'd be glad to help within the limits imposed by the 24 hour day and the demands by memmbers of our household who believe they own the computer. > Steven E. Mayer, Ph.D.