[ol'cs]

on what PD researchers SHOULD be looking into, in order to get to "the bottom" of the PD question, or fire up the run time to a "cure" or at least a "prevention".

MY first and foremost question is "what is killing DA neurons"? Is is stress, inflammation, built in genetically by some distant mutation, toxin(s), or WHAT. To me , we can take all the serendipitous shots in the dark we want, but very little progress will be made until we know WHAT is killing off these so very precious brain cells. Is it "one thing", a "host of things" or just WHAT. IMHO PD researchers should be focusing on getting PD neurons from cadavers, then , trying first just to keep them alive (ie; culture them; not easy). If colonies can be made either by using nerve growth factors and/or cloning. Then every possible cellular microprobe known (and others yet to be invented) should be used to try to answer the above question. As you guys and gals know, I fastidiously fly the transplant flag and would not be deterred from this line of inquiry just because my nice healthy in-vitro neurons kept dying.
We could take a lesson from macro-organ transplants. Newly transplanted livers don't get cirrhosis again if the tranplantee stops boozing, and new heart transplant patients don't suffer heart attacks if they stick to doctors orders (and got a good implant to start with. Today, almost any organ can be transplanted successfully. Why should it be so dang blasted difficult to be able to transplant new SN cells and not have them just die off on us like the old ones? We are doing something WRONG, and it seems that researchers are giving up too easy to make that something wrong, figured out. and made RIGHT.
If it's true that newly implanted SN cells are suffering the same fate as ones presently in place, then that's a clue. What it is saying (if we accept that the same factors are responsible for killing new SN neurons, as it did the older ones), then the FAULT is probably not within the cells themselves, but is due to an exogenous mechanism. Such a clue would suggest that the environment around the new neurons should first of all be "cleaned" of any obvious exogenous factors; "helped" by introduction of agents known to induce growth and survival; and "monitored" to see just what is happening in-vivo (radioligand(?) tagging of (?) to monitor intracellular health, needing lots of new ideas here.
On the other hand, scrap what i just said, and think of this idea! I wonder if mutated enzymes are producing very small quantities of an MPTP like specific DA neurotoxin, by some as yet undiscovered pathway. This would answer a lot of questions, such as PD before the industrial age and any newly introduced neurons being subject to the same fate as the old ones. That's what i'd do. i would look for very small quantities of a neurotoxin with a structure similar to MPTP in dead neurons. If something like this were found, all that would be neccessary to halt the PD process would be to find a specific enzyme inhibitor to this newly found pathway to this newly found neurotoxin.
Of course, if something other than PD is going to make humankind extinct in the near future, we should just eat what we want, drink what we want and just make merry!!!