As a newbie, I've been bringing myself up to date on Parkinson's research. There seem to be almost as many theories for the mechanism by which the disease develops as there are scientists working on it!
One paper which caught my eye reported in 2007 that drinkers of black tea (in Singapore) had about a quarter of the risk of non-drinkers of developing PD.
(http://aje.oxfordjournals.org/content/167/5/553.full#sec-6). This has probably been discussed in an earlier thread.
When I looked in Google Scholar for papers which followed this up I found there is some rationale being established experimentally to explain the protective effect of black tea. Apparently black tea contains theaflavins which are potent anti-oxidants. An Indian group has shown that theaflavins protect nigral dopaminergic neurons (in a test tube) against a neurotoxin known to induce Parkinson's like symptoms, a Japanese group that theaflavins stimulate autophagy (putting in the cell dustbin) of alpha-synuclein(a protein most suspected of being the initiator of cell death in PD) and a German/American group have shown (in the test tube again) that theaflavins stop alpha-synuclein from turning rogue.

What I am wondering out loud is, if these experiments really do demonstrate the molecular basis for the protective effect of black tea then surely the same effects should slow down progression of the disease too?

I'll make a cuppa and think about it...........

it depends whether the initial cause is the same as the ongoing cause. for example a virus could initiate an immune response which carries on after the virus has gone. if however the disease was simply caused by an external factor then the same action that reduced the chances of the disease starting could also reduce its ongoing activity.
my own belief is that pd has many initial causes but only one (or at most a handful) ongoing cause(s) in which case it is too late to shut the stable door as a self-perpetuating cycle has begun, and a spanner needs to be poked in its wheels.

Hi Bartobob

Interesting questions!

Quite a few lifestyle factors have been identified as reducing risk of Parkinson's including drinking tea or coffee, taking ibuprofen and smoking.

Earlier this month a small but interesting study was published that seemed to show that taking caffeine pills may slightly improve some of the movement symptoms of Parkinson's.

http://www.parkinsons.org.uk/about_us/news/news_items/all_news/a_coffee_a_day_for_parkinsons.aspx

But so far there's no evidence that any of these things can slow the course of Parkinson's in any significant way.

Best wishes

Claire
(Research team)

Several cups of black tea later.........

Yes, Turnip, there may be 2 phases to the disease, an initial conversion event and then a self propagating progression. A plausible sequence of events which is being shown experimentally is:

the transformation of alpha synuclein protein into a toxic form in the splanchnic nerve of the gut (no experimental evidence yet);

migration of the toxic alpha synuclein initially to the brain stem (experimental evidence);

propagation of toxic alpha synuclein in a progressive manner from the brain stem to several regions of the brain (experimental evidence). Experiment and neuroanatomical studies have shown that toxic alpha synuclein protein behaves like a prion (an agent of infection);

Once in the neuron the toxic form of alpha synuclein causes natural alpha synuclein present to convert to the more toxic form.(Experimental evidence)

The neuron's rubbish disposal systems cannot cope with the sudden build up of toxic protein and the cell dies.(experimental evidence?)

The toxic prion disrupts cellular membranes either by sitting in them or by switching off production of their components. Inability to make energy and maintain cell internal environment ensues and the cell dies. (experimental evidence)


Theaflavins have been shown to interfere with the transformation of natural alpha synuclein into other forms ans also to stimulate autophagy (rubbish disposal). So they could in theory be acting at the initial conversion event in the gut or on the progressing disease in the brain. However I suspect the concentration of thiaflavins achieved in the gut by a cup of black tea is more biologically relevant than that achieved in the brain. It would be interesting to see the effect of theaflavins (at the level found in the CSF) on infected neuronal cell systems like those used by Desplats et al. to test the possibile effects on cell death. (http://www.pnas.org/content/106/31/13010.full)
So yes, on reflection my gut feeling is tea is probably preventing the initial disease event..............

Thanks Claire for the info on other agents that affect Parkinson's symptons.

Continuing with my sudden interest in slowing down Parkinson's ..........
Zheng et al.(http://stm.sciencemag.org/content/2/52/52ra73.abstract) have identified PGC-1alpha, a master gene regulator protein which has been found at unnaturally low levels in the brains of PD patients. Fortunately a family of compounds in use to treat diabetes(such as Avandia or Actos) is known to switch up this regulator. These compounds were subsequently shown to protect cells (in the test tube) against a neurotoxin which causes PD symptoms (http://www.nature.com/news/2010/101006/full/news.2010.518.html#B1).
One of these compounds is in clinical trials to determine if it will slow down PD in people (http://www.bidmc.org/CentersandDepartments/Departments/Neurology/ParkinsonsDiseaseandMovementDisorders/ResearchandClinicalTrials.aspx)or if it will stop dyskinesia induced by L-Dopa (https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=678). Results eagerly awaited!

.....Parkinson's UK is sponsoring research studying pGC-1alpha in fruit flies, looking for other compounds which turn it up. (http://www.parkinsons.org.uk/pdf/H-1105_Partridge_plain-english-summary.pdf)

The link in the second paragraph of my last post should read:





(http://www.bidmc.org/CentersandDepartments/Departments/Neurology/
ParkinsonsDiseaseandMovementDisorders/ResearchandClinicalTrials.aspx)

very interesting Bartobob
i had never come across the idea that the alpa-s could go toxic (misfolding?) outside the brain first. Personally i would bet on the nose rather than the gut, but i suppose there's no reason it can't be both?
one thing that is encouraging is how much more detail there is on the wikip page
http://en.wikipedia.org/wiki/Alpha-synuclein
the scientists are really getting a very detailed picture of the mechanisms, hopefully coming up with some way of stopping it.

Yes Turnip, the nose, tongue or eye might be rich access points for a toxin to transform alpha-synuclein. If Parkinson's is a prion disease, do cannibals have a higher incidence?

Anyway, three exciting clinical studies looking at slowing down Parkinsons:

Actos(Pioglitazone) which switches up PGC-1alpha as described in my last post has a phase 2 clinical study (phase1-is it safe?,phase2 does it have the right effect?, phase3 what best dosage?)finishing at the end of this year.

Cogane, a plant derived compound which stimulates the growth of new nerve cells in the brain (http://www.phytopharm.com/index.php?option=com_content&view=article&id=45&Itemid=31) and is being tested for slowing the disease down,finishes its phase 2 study at the end of this year too.

Preladenant an adenosine 2A (A2A) receptor antagonist (shuts down those brain cells which stimulate the substantia nigra)developed by Schering-Plough is recruiting to test its efficacy to stop L-DOPA induced dyskinesia in a phase2 study.

I've seen a lot of clinical trials produce disappointing results but I am definitely faintly optimistic that one or more of the above will be successful!

Don't think there is any correlation between cannibalism and pd, or at least no-one on the forum has mentioned having partaken. There used to be cannibals in Guam where there is Lytico-Bodig disease but that might be from eating poisonous fruit bats. Or perhaps the old ways are still being practiced in secret!

Am I correct in thinking that these studies of the role of toxic alpha-synuclein (and hence the potential benefit of black tea in it's role as an anti-oxidant as opposed to something which stains your tea cup , as a preventative measure rather than a treatment for Parkinson's ) relates to familial or sporadic PD, and not the far more prevalent idiopathic PD?