[lurkingforacure]

Apparently it "spreads" cell-to-cell, but I cannot reconcile this study with the research I have read which indicates the alpha-synuclein clumps result from a genetic defect in the folding process. Here's this link:

http://www.sciencedaily.com/releases...0727191914.htm

[vlhperry]

Dear Laura,

The dopamine produced by the dopamine producing neurons in the substantia nigra pass through mitochondrial pathways to reach the nerves to send messages to the muscles to move or not. I am not sure how lewey bodies play a role in genetic forms of Parkinson, as the study I read of families of genetically related PD, the majority of patients did not have the lewey body disease that other Parkinsonian patients have. Alpha synuclean protein did block the pathways, causing the dopamine to back up into the substantia nigra, after which the overabundance of neuron producing dopamine cells became apoptic or suicidal.

I believe even if the understanding of what causes PD could be understood, there may not nesccesarily be a cure. We can only hope. But we should also be prepared for that possibility and accept what science offers now to improve our quality of life.

[caldeerster]

I'm not going to "accept" what science is offering us now, because, frankly science can do far better with this disease, and I belleve they are finally on the verge of doing so. EVen if a "cure" remains elusive for a number of years, if researchers can learn how to disaggregate alpha synuclein and if they can slow or stop the inflammatory process which causes cell death, the disease then becomes a chronic, NON-degenerative condition, which I think all of us would welcome as a huge step forward. And I don't think that is unachievable in the relatively near future.

caldeerster

Originally Posted by vlhperry

Dear Laura,

The dopamine produced by the dopamine producing neurons in the substantia nigra pass through mitochondrial pathways to reach the nerves to send messages to the muscles to move or not. I am not sure how lewey bodies play a role in genetic forms of Parkinson, as the study I read of families of genetically related PD, the majority of patients did not have the lewey body disease that other Parkinsonian patients have. Alpha synuclean protein did block the pathways, causing the dopamine to back up into the substantia nigra, after which the overabundance of neuron producing dopamine cells became apoptic or suicidal.

I believe even if the understanding of what causes PD could be understood, there may not nesccesarily be a cure. We can only hope. But we should also be prepared for that possibility and accept what science offers now to improve our quality of life.

[Conductor71]

Originally Posted by caldeerster

I'm not going to "accept" what science is offering us now, because, frankly science can do far better with this disease, and I belleve they are finally on the verge of doing so. EVen if a "cure" remains elusive for a number of years, if researchers can learn how to disaggregate alpha synuclein and if they can slow or stop the inflammatory process which causes cell death, the disease then becomes a chronic, NON-degenerative condition, which I think all of us would welcome as a huge step forward. And I don't think that is unachievable in the relatively near future.

caldeerster

I love your attitude! I'm hoping that the research conducted at Columbia this April showing the link between dopamine, a calcium channel, and alpha-synuclein goes somewhere. Isradipine, the calcium channel blocker, showed a slowing of disease progression in animal models. Sounds like at the very least a possible new treatment to slow things down and buy us more time.

http://www.eurekalert.org/pub_releas...-pnd042309.php

Laura

[vlhperry]

http://content.nejm.org/cgi/content/full/342/21/1560

Consortium
On
Risk for
Early-onset PD

[reverett123]

What causes PD? That's like asking what causes a broken leg. Your chart is different than mine, but we are both in casts. I stepped into a hole. You stepped in front of a bus. In both cases a force was applied to a bone that exceeded a critical limit.

Other factors had a lesser role. I drank sodas all my life and my bones were brittle and one broke. Your genetics favored strong bones, else you might have died.

The guy in front of me was lucky and missed the hole by an inch. Can you accept bad luck as causal? Or is it better to call it chance?

And what if you had stepped out your door thirty seconds earlier? No bus. Sensitivity to initial conditions. Non-linear systems. Chaos generates reality. Unless you are a mathmatician I probably lost you there.

There is no cause for PD. Instead, there are a dozen factors which can add to your chances of getting it. Rack up the necessary total using any combination and you "win".

Some factors count more than others. Immune challenge in the womb is big. And it comes with bonus points if you draw the Pesticides card later in the game. The time your Great Grandma was frightened by a mouse counts, too. Just a little. But it really does. How complicated is it? Very. You can do a lot with twelve variables. Look here.

So much for "A" cause. So, what IS PD? A collage of motor symptoms from immune cells damaging our substantia nigra because your fetal immune system was challenged. And that mouse that scared Gran ultimately gave you an endocrine system that reacts to stress a certain way. And peptides that might have kept you healthy and normally manufactured in the gut simply were not, due to the microflora living there or not.

Stressed systems wear down and eventually collapse. Somewhere along that journey you notice that you are "jumping out of your skin" at little sounds. And your tremors really take off. So do the other symptoms, motor and non-motor. Stress increases symptoms which increase stress which.... That's called a feedback loop and amplifies things quickly and leaves you in a heap on the ground.

Are we doomed? Not by a long shot. We just have to think about PD differently.

One of those ways is what I call "process theory." Just as there are a dozen or so causal factors, there are a half-dozen or so processes at work which eventually result in PD. Affect one of them and your symptoms improve or show up later. Affect two? Three? and progression is stopped. Four? Five? and your body's repair systems get a chance.

We know most of those processes. Inflammation. Oxidation. Microglial activation. Chronic stress. Mis-folded proteins. We need to work out the list a bit more.

We know, too, ways to halt or mitigate many, if not all, of these. Turmeric. Fish oil. Green tea extract. A dozen more.

That is the bare bones version of what Anne Frobert and I put thousands of hours into figuring out. It comes mighty darned close to explaining 90% of PD.

There is no one cause. There is no one cure. But multiple lines of damage provide muliple lines of opportunity to slow, halt, even cure. "It's not a bug, it's a feature!"