One interesting thing about Parkinson's disease is that although dopamine is produced in several areas of the body including the brain in the substantia nigra and the ventral tegmental area, the VTA does not appear to be susceptible to over-expression of alpha synuclein. Which means there is yet another research area for the potential of grafting - or stem cell therapy. Moreover, not that much dopamine is metabolized to norepinephrine which explains why PD may not begin officially until the number of norepinephrine neurons also diminish.
But that's not our question for today. What do we know know about saving dopamine neurons in the substantia nigra?
Mouse PD models have already demonstrated that cell "rejuvenation" protects neurons in studies at Northwestern University. Most human cells use either potassium or sodium channels when they are young but as the body ages, the dopamine cells switch to calcium channels. By blocking the calcium channel may give the cell a chance to rest and recover which is healthier than cell death and essential for PD. In 2007 Steve read at least two abstracts by Dr DJ Surmeier etal about this very subject.
In order to stay on target we have to mention the arguments.
In the study entitled "Interplay between Cytosolic Dopamin(e), Calcium, and alpha-synuclein causes selective death of Substantia Nigra Neurons"
"They attribute this specific elevation of cytosolic dopamine in SN neurons to the presence of a pace-making L-type calcium channel as a source of calcium entry, present in SN, but not VTA, neurons. Blockade of this channel, as well as treatment with intracellular calcium chelators protects SN neurons from cytosolic dopamine build-up....the pace-making L-type Ca channel may prove to be a useful therapeutic target in PD"
action potential which opens the Ca channels. So what we need is a way to prevent the floodgates from opening to cause that neuron damage.
Of the dihydropyridine class (note that they all end in "dipine"), the L-type inhibitors which cross the blood brain barrier are: Amlodopine, Azenlnipidine, Clevidipine, Felodipine, Isradipine, Nicardipine, Nefedipine and Nimodipine.
A unique interactive brain diagram thanks to Open Colleges
April is Parkinson's Awareness Month
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