Chemical That Triggers Parkinson's Disease Discovered
 

See
http://www.sciencedaily.com/releases...1030153020.htm
where it claims dopal (3,4-dihydroxyphenylacetaldehyde) causes PD.

"The SLU researchers discovered that dopamine itself actually plays a role in destroying the cells that produce it.

In the process that leads to Parkinson's disease, dopamine is converted into a highly toxic chemical called DOPAL. Using test-tube, cell-culture and animal models, the researchers found that it is DOPAL that causes alpha-synuclein protein in the brain to clump together, which in turn triggers the death of dopamine-producing cells and leads to Parkinson's.

"This is very exciting," Burke said. "This is the first time that anyone has ever established that it is a naturally occurring byproduct of dopamine that causes alpha-synuclein to aggregate, or clump together. It's actually DOPAL that kicks this whole process off and results in Parkinson's disease."

I am sure this has been proposed before, for example see below.


Li SW, Lin TS, Minteer S, Burke WJ. 2001. 3,4-Dihydroxyphenylacetaldehyde and
hydrogen peroxide generate a hydroxyl radical: possible role in
Parkinson's disease pathogenesis. Molecular Brain Research 93(1):1-7.
Abstract: 3,4-Dihydroxyphenylacetaldehyde (DOPAL) and 3,4-
dihydroxyphenylglycolaldehyde (DOPEGAL), the monoamine oxidase
(MAO) metabolites of dopamine (DA) and norepinephrine (NE),
respectively, are toxic to catecholamine (CA) neurons in vitro and in vivo.
DOPEGAL generates a free radical and activates mitochondrial permeability
transition, a mechanism implicated in neuron death. To determine if DOPAL
and other DA metabolites generate the hydroxyl radical in the presence of
H2O2, we used HPLC-EC to detect salicylate hydroxylation products. To
determine the relative reducing capacity of DOPAL and DOPEGAL we used
cyclic voltammetry to measure their reduction potentials. Results indicate
that DOPAL, but not DOPEGAL, DA or other DA metabolites. generates
hydroxyl radicals. Atomic absorption spectroscopy and heavy metal
screening indicate that this result is not due to contamination of DOPAL with
iron or other heavy metals. DOPAL reduction potential ( 161 mV) is lower
than that of DOPEGAL (235 mV). DOPAL is present in human substantia
nigra. The implications of these findings to CA neuronal death in
degenerative brain diseases are discussed. (C) 2001 Elsevier Science B.V.

Does this imply that PD could be an immune system disorder once the initial insult occurs? Whatever that may be?

Or autoimmune?

paula

If this research is true then ...
 

doesn't it mean that taking l-dopa will make us worse ?

I thought we had all agreed l-dopa does not make us worse, (thats "we" as in the royal "we") !

Have I missed the point ?

Neil.

I don't think anything has been proven......the more we discover, the more we realize we don't know. I know i have to take l dopa to function. If it also is harmful to me, wouldn't that be an immune problem?

REPEAT - in over my head. What, or who, is the royal we? My deformed little brain is overtaxed I fear.

paula

Paula ...
 

The royal "we" (Pluralis Majestatis) is the first-person plural pronoun when used by an important person to refer to himself or herself. Its best known usage is by a monarch such as a king, queen, or pope. It reflects the fact that when a monarch speaks he or she speaks both in his own name and in the name of his function, office or status.

Most famous quote is Queen Victoria's "we are not amused", (referring to her own lack of amusement).

From climate change / Al Gore, to rugby, to PD as an (auto)immune condition, to English personal pronouns, we sure are covering a lot of ground with our typically incisive wit and drive :)

Neil.

Oh i see, like patronizing nurses in the hospital or nursing homes...how do we feel this morning? are we hungry?

only minus the royal.

thank you Neil.

Off topic ... (my original query re. l-dopa was a serious one) ...
 

No Paula that is called "the patronizing we", (no kidding), sits alongside "the editorial we", common in scientific literature, referring to a generic third person by "we" instead of the more common "one" or the informal "you":

e.g. "By adding three and five, we obtain eight".

Something to discuss with your partner tonight !!

Neil.

Dopal
 

Hey fellas, I am just reporting this, I haven't a clue whether it means we should not take l-dopa etc. If you think about it, healthy people have plenty of dopamine compared to our meagre supply. So why haven't they got PD and we haven't!!! (joke) Go figure.
It just seemed a relevant interesting paper. Dopamine is synthesised also in the body, and acts as a hormone. However, I guess the authors here are talking about processes in the brain, not in the body.
The more I post, the more trouble I get into!!! LOL
Ron

No Ron , you aren't in trouble. I'm looking for my UDall meeting book where I recall they spoke about it being something else. If I find it I will post about it.

Paula

It all goes back to the Mitochondrial Pathways
 

As it was explained to me, the dopamine pathways back up leaving no where for it to go so it begins to destroy itself. Levodopa can get through the blood brain barrier and substitute, though it be not as efficient as dopamine.
Which is why it is so hard to stay on an even keel. Too much levodopa and you add to the damage; not enough and you can't function. What role the other drugs play, I am not sure of.

This information was first reported in the pathological study of patients who had a Parkin malformation.

1. Reviews in Neurological Diseases, Vol 1, No 3., 2004, author John J. Kelly, M.D., The George WashingtonUniversity Medical Center, Washington D.C.
"Researchers from Switzerland, studied a more common, recessive form of inherated Parkinson's disease that typically strikes before the age of 40 and is linked to a mutation in the Parkin gene. The loss of enzyme activity resulting results in an accumlation of protein substrates, including alpha synuclein, in the cell. In these juvinile Parkinson's cases, lewey bodies do not generally present.

In these forms of the disease involving buildup of alpha synuclein in the cell, would result in degeneration and death (of the cell.)

Paula, this is what the GDNF factor was about. By combining a virus and Parkin and delivering it into the cells, protected the cells from neurotoxicity.

2. "Protecting microtubule "highways" may lead to novel therapies", Medical Neurology, 12.6.2004 states that Parkinson's disease may be caused by a double whammy; mutated Parkin genes combined with the highly toxic chemical rotenene, results in a cascade of highly toxic free radicals, the destruction of microtubules that transport dopamine to the brain's movement center, and eventioal death of the dopamine producing neuron.

3. "Progression of nigrostriatal dysfunction in a parkin kindred: an [FDOPA PET and clinical study. MRC Clinical Sciences Centre, London, England. Received November 21, 2001, Revised March 27, 2002, Accepted April 24, 2002.
"Neuropathology of Parkin cases is limited but, in cases that have been reported, there was a generalized loss of dopaminergic neurones in the substantia nigia pairs compacta without Lewy body inclusions. ...subclinical nigrostriatal dysfunction has been demonstrated in carriers of a single mutent parkin allele (Hilker et al, 3001). RESILTS <eam age pf pmset su,[tp,s was 29 uears (ramge 28 - 32 years). All affected siblings ha a striking response to L-dopa therapy, with levodopa-related dyskinesias after a mean interval of 2.4 years. Estimated mean clinical disease was 26 years (range 19 - 32 years) at the time of the second scan. The clinical presentation of the patients was comparable with that of juvenile-onset parkinsonism; however, currently their phenotype was indistingshable from IPD, with a common feature of severe resting leg tremor.

4. "Parkin Stabilizes Microtubiles Through Strong, Binding Mediated by t=Three Independent Domains."" The American Society for Biochemistry and Molecular Biology. From Department of Physiology and Biophysics and Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY

5. Parkin counteracts symptoms in a Drosohila model of Parkinson's disease.
Annika FM Heywood and Brian E. Staveley, Univerisity of Newfoundland, Department of Biology, St. John's, Newfoundland and Labrador, Canada. Publlish 16 April, 2004. BMC Neuroscience.
Conclusions: Our experiments demenstrate that the directed expression of the parkin gene counteracts the PD-like symptoms."

6. Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism, Brain Vol 127 No 6, 2004.

Tired of typing. Going back to bed. I have followed this trail of infor for many years.

Sincerely,
Vicky