the same molecules that are killing our SN neurons are the result of a "transfect" of an intracellular process. Much in the same way that gene therapy relies on the transfer of specific bits of genetic information into a cell to "turn on" some "good process", we are getting gene transfer from compromised cells to "clean" cells.
A long time ago, it was suggested that dopamine itself was the culprit itself. Much work suggested that this was not true. But then we now have something staring us right in the face so to speak. It all began with the discovery that some molecules which are structurally related to dopamine are actually potent killers of DA neurons. One of them particularly intrigues me. This molecule isx 6-hydroxy-dopamine. It is just too simple! The addition of another hydroxy group at the 6-position of the aryl ring in dopamine, turns it into a "killer" molecule.
THis has been proven by the fact that 6-hydroxy-dopamine is used in laboratories to "give" rats a parkinsonian condition, known as the "contralateral rotation test" This test is done by injecting this molecule (or the use of MPTP, or a few other known specific SN cell killers) into one of the two SN structures (these SN structures occur in both "halves" of the brain). After some time has past (a few short weeks), the animal is PD compromised on that side of the body. The animal is always "hemiparkinsonized" never "globally parkinsonized" because only one piece of the dopamine producing SN has had a majority of it's cells killed off because only one side is injected with the toxin.
Now comes the part thati am not sure of. Does anyone know if hey have kept these rats alive long enough to see if "Globalization" occurs? That is, does the experimantal "parkinsonization" of one side of the brain "spread" to affect the other side, and most important, if it does, how and why does it do this?
Ever since i learned of this "supertoxic parkinsonizer", 6-hydroxy-dopamine, i said to myself "it's so very similar in structure to dopamine, just one simple little hydroxy group attached at the 6-position of the dopamine aryl ring, why is it so effective in the killing of DA neurons? Well, i won't get into the proposed mechanism, but the fact remains, 6-hydroxydopamine selectively kills off DA neurons.
So, we have something right in our hands , right now, that we know causes PDism. MY question has been out there for years now. IT is " do we have an enzyme which by mutation of that enzyme, results in an isozyme that can 6-hydroxylate dopamine" This would be the "cause of PD" as i see it. Maybe the enzyme is very inefficient at performing this chemical transformation, so something has been missed in the extensive studies of the question of whether dopamine itself is at the root of PD. Maybe it does it's dirty work only in the presence of specific low concentration co-factors,and has thus been missed, because only attomolar concentrations of 6-hydroxydopamine are produced and are at this concentration indetectable, but nevertheless remains the true "root of PD".
Thus, any healthy DA neuron isn't safe in the presence of this almost indetectable process. You can put new cells, but you haven't addressed the question of protecting them from this insidious "cloaked" killer.
If we could trace this molecule (or something similar to it) as teh "Silent kiler of DA neurons", then we could have a shot at halting or with the implant of healthy cells , reversing the process of the continuing neuron loss that is PD.
REmember, we all lose a small percentage of DA neurons every year of life, but us PWP lose too many too quickly. This fact fits right in with a "slow silent killer" whose rate of DA neuron destruction is different for everyone.
IMHO, this is not too difficult of a biochemical detective story. Give us a lab, hire a few of the world's best biologist and chemist post-docs, a toxicologist, maybe a brain surgeon, and a top of the line GC-LC MS operator, and other things like capillary electrophoresis as tools and a few pathologists and they could have an answer to this question. This would go a long way to get at the "heart" of PD. cs