[paula_w]

Olsen posted this in another thread; Jaye spoke of Langston in another thread too. I'm adding forum notes to this theory.

Neurosci Lett. 2007 Jan 14; [Epub ahead of print] Related Articles, Links

Abnormal levels of prohibitin and ATP synthase in the substantia nigra and frontal cortex in Parkinson's disease.

Ferrer I, Perez E, Dalfo E, Barrachina M.

Institut de Neuropatologia, Servei Anatomia Patologica, IDIBELL-Hospital Universitari de Bellvitge, Facultad de Medicina, Universitat de Barcelona, Hospitalet de Llobregat, Spain.

Prohibitin and ATP synthase protein levels were examined in the substantia nigra and frontal cortex (area 8) in five cases of Parkinson's disease (PD), five cases of dementia with Lewy bodies pure form (pDLB), five cases of early Alzheimer's disease (AD stage IIA, B), nine cases with advanced AD (stages V/VIC), and nine controls. A significant reduction of prohibitin and ATP synthase was observed in the substantia nigra in PD cases. In contrast, increased prohibitin and ATP synthase levels were found in the frontal cortex in PD, and increased prohibitin but not ATP synthase in the frontal cortex in pDLB. Superoxide dismutase 2 (SOD2) expression levels were also increased in the frontal cortex in PD and pDLB. No modifications in prohibitin and ATP synthase levels were found in the frontal cortex in sporadic AD. These findings demonstrate disease-specific modifications in the expression of mitochondrial-related proteins in the frontal cortex at stages of PD in which there is no alpha-synuclein aggregation in the form of Lewy bodies and Lewy neurites in this area. These findings emphasize the presence of mitochondrial modifications before the appearance of histological hallmarks of PD, and point to the possibility of a more extended molecular pathology in PD than currently accepted.

PMID: 17284347 [PubMed - as supplied by publisher]

==============

The forum talk given by Dr. Bill Langston, the guy who realized that a synthetic forum of heroin could be used as a PD model in animals, thus enabling research, clarified some things that have been talked about as precursors of PD as actually the early stages if the disease itself, thus eliminating the substantia nigra as being the point of origin. He speculates that it could begin in the brain stem, [this slide included a picture of the Vagus nerve], the gut, and other places. He thinks it then [from the substantia nigra] moves on to the cortex. [I don't have a handout and we heard this speaker over lunch so those with the handout chime in here].

Thus, loss of smell and constipation in a PD patient are actually the disease itself in early stages because they are symptoms, not precursors. By the time you get to motor symptoms, it could be too late and much further down the line than the beginning of the illness. He bases his theory on the presence of Lewy bodies, which are clumps containing the protein alpha synuclein. He said the normal person has two expressions of nuclein and a PD patient has double that. Lewy bodies do not only appear in the brains of PD patients in autopsy, but also in the gut and several other areas. Therefore over expression of nuclein is a major factor.

There is more and I don't remember it all so will stop here. We do not know the purpose of normal nuclein expression. Whoever discovers that, will possibly hit a jackpot.

Langston even suggested possibly changing the name of the illness itself, offered perhaps the name Parkinson Lewy Disease, as he feels that Lewy's work is as significant and that a much expanded definition of the illness is needed.

Other highlights: Duopdopa trial coming to the U.S. this summer rather than the originally reported January of this year. The lady from Europe who spoke wasn't sure if it was phase II or phase III because she "doesn't understand the FDA." This treatment holds much promise for evening out symptoms.

A provocative new theory involving calcium channels was presented but I have to check notes on that before posting.

Interesting fact: James Parkinson, after whom the illness was named, thought the illness was caused by stress.

[lou_lou]

That was a great synopsis!
Dear Paula,
I agree with Dr. Parkinson
stress is the first step down for all disease...
I believe that to be true in my life...
trying to stop -the stessed out thinking -and instill calm and peace,
try it. you may find it helps...

[michael7733]

sorry, Paula. my post was inapropriate here.

Excellent reporting. Keep up the good work.

michael b.

[reverett123]

Paula-

Did Dr. Langston by any chance give any credit to Dr. Braak of Germany who has been pushing this theory for over five years now?

-Rick


The forum talk given by Dr. Bill Langston, the guy who realized that a synthetic forum of heroin could be used as a PD model in animals, thus enabling research, clarified some things that have been talked about as precursors of PD as actually the early stages if the disease itself, thus eliminating the substantia nigra as being the point of origin. He speculates that it could begin in the brain stem, [this slide included a picture of the Vagus nerve], the gut, and other places. He thinks it then [from the substantia nigra] moves on to the cortex. [I don't have a handout and we heard this speaker over lunch so those with the handout chime in here].

Thus, loss of smell and constipation in a PD patient are actually the disease itself in early stages because they are symptoms, not precursors. By the time you get to motor symptoms, it could be too late and much further down the line than the beginning of the illness. He bases his theory on the presence of Lewy bodies, which are clumps containing the protein alpha synuclein. He said the normal person has two expressions of nuclein and a PD patient has double that. Lewy bodies do not only appear in the brains of PD patients in autopsy, but also in the gut and several other areas. Therefore over expression of nuclein is a major factor.

There is more and I don't remember it all so will stop here. We do not know the purpose of normal nuclein expression. Whoever discovers that, will possibly hit a jackpot.

Langston even suggested possibly changing the name of the illness itself, offered perhaps the name Parkinson Lewy Disease, as he feels that Lewy's work is as significant and that a much expanded definition of the illness is needed.

Other highlights: Duopdopa trial coming to the U.S. this summer rather than the originally reported January of this year. The lady from Europe who spoke wasn't sure if it was phase II or phase III because she "doesn't understand the FDA." This treatment holds much promise for evening out symptoms.

A provocative new theory involving calcium channels was presented but I have to check notes on that before posting.

Interesting fact: James Parkinson, after whom the illness was named, thought the illness was caused by stress.[/QUOTE]

[AnnT2]

Paula -

Thank you for your summary. It was very clear.

This may be a dumb question, but what are Lewy bodies exactly? At autopsy, are they microscopic or visible to the naked eye? Are they uneven growths, like a tumor, or are they smooth like those bubbles in tapioca? If they are present in other places, are they palpable?

Thanks.

Ann

[paula_w]

Rick,

Yes absolutely. Quoted him throughout and I wrote the above from memory so that's my omission. Haven't even unpacked my notes yet. I copied Olsen's post because it was similar but I didn't want to put a PAN summary in her thread. More coming....just woke back up.

Ann, Tena, it's always a pleasure to share the news....and we all knew PD had to be more than it is being defined.

Michael, I remember the night you wrote that but afraid I'm going to have to read it again WITH coffee to understand a few words of it lol. But you have been working on mitochondrial theory all along - I think I understand a little bit of it at best.

More coming. Ann, as a lay person I can tell you Lewy bodies were brown in Langston's slides..lol. But he didn't tell us till the end, that one picture was from the brain. All the other pictures on that slide of Lewy bodies were from elsewhere in the body. They contain protein that is over expressed and I don't want to venture more without unpacking the notes.

Paula

[vlhperry]

I have PD too. Consider the following two studies:

http://molecular.biosciences.wsu.edu.../pall_main.htm

http://neuroscience.jhu.edu/TedDawsonrecentpapers.php

Love,
Vicky

[paula_w]

Vicky,

I have an in-law with this syndrome that doesn't have a single name. It's been extremely frustrating for her entire family as some days she can't get out of bed. She has sought treatment in various places. Are you saying that you have PD also along with this when you say "I have PD too?"

paula

[vlhperry]

Paula,

Did you read my links?

Vicky

[paula_w]

I skimmed your links - haven't read every word. Am I missing something? My response was about the first one involving the condition of multiple syndromes including chronic fatigue, fibromyalgia, et al.

I haven't begun to unpack, and will be like a vegetable for several days so can you be more specific about why you are asking......I'm not too bright at the moment. I see that the second one involves alpha synuclein theory and I do understand that alpha synuclein in excess is not a new theory. I think the purpose of Langston's talk was to take what information is known and officially redefine PD as more than a set of motor symptoms when it is diagnosed and hopefully result in a multicisciplinary approach. He said that by the time the neurologist sees us it could be well advanced.

Everyone is a specialist, so much is being missed in terms of diagnosing PD. He acknowledged the genetic 'families' with PD, but feels they account for a small percentage and when looking at all of the research, suggests that PD may not be a single disease. Again not new, but convincing the medical community to recognize this officially will probably take years.

paula