Why is PD Chronic and Degenerative?

Can anyone explain why pd gets worse and is chronic?

If pd is caused by alpha synuclein protein clumps in the brain why do they continue to form no matter what people do such as exercising, taking anti-oxidents, eating well, etc. ?

There is a lot mentioned in pd literature about slowing the progress of pd? Is this possible? If it is then why can't it be stopped? Doesn't make sense that you can slow something (a positive impact) but can't stop it from going worse?

Nicotine, for example, is thought to be neuroprotective, one assumes that if this is correct, can it actually stop pd from going worse?

Also a high fat diet is thought to be good for the brain. I am going for a fry-up and a smoke.

99 Replies

  • Does anyone think they have slowed the progress of pd? Why and how?

    Also why are some prescribed Azilect for the neuroprotection and others not?

  • The studies on azilect are contradictory. So even that is not necessarily effective in slowing the progression.

  • Yes, it is unclear about Azilect. Nicotine does seem to reduce the chance of pd but hard to tell the amount. In France it seems more common to prescribe nicotine patches and I know someone who uses them and is convinced they are beneficial. This would seem to indicate that neuro protection is possible on some level. It is said coffee is neuro protective - not sure about this, that anti-oxidants help also.

    Do you think it is possible to slow its progress?

  • Stop or reverse Parkinson's? Sure, easy! Just tell me how we can stop aging and I'll tell you (with equal veracity) how to cure PD.

    It is only possible to slow down or stop something reliably: a) once we understand the cause-effect sequence, and b) have all the practical prereqs (technical finesse, power, material, time, etc.) to make it happen. In the case of Parkinson's, we don't even have item a), and until we have a), item b) is not even a pipe dream. (OK,it's not always so systematic. Lots of times in medicine, a successful methodology (b) is discovered by accident before we understand how it works (a). We can always dream that someone's granny will hit upon a recipe for chicken soup that cures PD :) )

  • when I was first diagnosed with PD 10 years ago,I came away full of hope of a cure being found in the near future, have been given an assurance by my then neurologist that Stem cells would bring about a complete cure "within the next 5 to 10 years". some nine years later I was informed by another neurologist that a "stem cell cure is light-years away". he told me to to place my faith in DBS (which I have subsequently learned is not a cure nor is able to slow down the progression of the disease). Still trying to be positive I underwent a full suitability assessment and was told that I was below the level of certainty of any benefits being had from DBS, but, if I wanted to have it done they would do it they would do it. I was told there were no other alternatives given that I am on the maximum dosage of just about every PD drug available (except for one which I feel could be of the most benefit to me i.e. Rytary, but which is not available in the UK as it is too expensive).

    And, to complete the picture, I was also prescribed Resagaline (Azilect) on the basis that it would slow down the progression

    so, dear Ozie, Dumpelkin and everyone else asking this question, I'm afraid that progression and degeneration seem to be the hallmarks of this rotten disease - because, since the invention of L-Dopa some 50-odd years ago all subsequent developments in Parkinson's medication has been to do with treating the symptoms rather than curing the disease itself. I'd love to be proved wrong and for someone to tell me that, if not a cure then at least some kind of drug to slow down or even reverse its progression is just around the corner. I know it would give me and no doubt all of you some positive for the future which we so desperately need.

  • Yitzbendovid,

    Well said! There are always whispers and murmurings that keep our flickering hope alive: mannitol., cinnamon, coconut oil, LDN, CoQ10 . . . One venerable spiritual tradition counsels that "surrender to God" puts an end to ALL problems by lifting us above them. But which of us has the discernment, detachment, and resolute will/intellect required to do that? If one of us had accomplished that, he wouldn't be schmoozing on this site! Or, if he shared his success in that department, many here would attack him with a firestorm of ridicule and invective! For good or ill, this is not a site for entertaining otherworldy solutions, no matter how effective they may be.

  • I had DBS, it has enhanced my life, no doubt about it. I have long accepted there will no cure, or slowing down of PD in my lifetime, I am 60yrs old now. As levedopa was discovered in the early 1960's it seems unlikely there will be a cure shortly. Also , they need to find the cause, before they are able to find the cure.

  • I think I have with fairly vigorous daily exercise. People who haven't seen me for some time say I look "better" - maybe better than they expected me to! Diagnosed 5 years ago. See local TV report.


    ( scroll to 9 minutes)

    But it's also a tyranny, because I feel I am on show and I can't drop my guard, for their sake too.

  • I asked my neuro about Azilect and she said "hocus pocus."

  • Do you think it is possible to slow pd down?

  • Very encouraging! I think that sometimes even very clever people should make sure they put their brain into gear before engaging their tongue.

  • My brother's movement disorder neuro also doesn't think much of Azilect. He is head of the department at the University of PA.

  • I don't understand why. It makes perfect sense - it stops your body from re absorbing excess dopamine, leaving it available for the body to use.

    It had a huge positive effect on me a few weeks after starting it.

    My neuro also said it wouldn't help the symptons, but he'd take it if it was him for it's possible neuroprotective effect.

  • Azilect does as you describe but unfortunately it isnt stopping your neurons dying though it may be slowing the process. Very hard to prove as you can imagine. We need dopamine neurons to produce the dopamine. When diagnosed they say we have only about 30 % left that work, the rest have died over the previous 10 - 20 years and they keep dying.

    I guess thats why PD is chronic and degenerative. They havent been able stop this happening because we havent yet got a full answer to why / how they die.

    We do know exercise is helpful but not exactly why and which type, there are studies on that at the moment. But exercise alone hasnt cured Parkinsons, look at all the athletes who have PD.

    I dont think the cure will be through meds, they might help by slowing down or stopping progress but there is the problem of getting them into the brain through the blood brain barrier - the body's way of protecting the brain.

    That means surgery and thats a long slow process to find the right substance and then to prove it is safe and effective.

  • clinicrowd mannitol might help

  • It might?

  • an isreally scientist discovered it helped in trials on mice restore the damaged area in the brain ..if u put in the link..clinicrowd mannitol u get the information re this

  • Well, on one hand it's anyone's guess, because who knows how slowly or quickly the disease would progress without any given intervention? However, studies have shown regular, vigorous exercise can relieve PwP of some symptoms, or the severity of symptoms.

    Google Rock Steady Boxing. It was started by a lawyer in Indiana who felt himself going downhill pretty fast until he started to hit the gym with a fellow lawyer (and former Golden Gloves champion). After about six weeks, he found he had regained many capabilities! He started Rock Steady Boxing for PwP and it's now in many states, the U.K., New Zealand and more. I go three times a week if I can.

  • It seems then that exercise might help us manage the symptoms better by being more generally physically effective but it doesn't slow the loss of dopamine producing cells? Or does it?

    Some like RSB, others cycling, crossfit, fast walking..............

  • Always the answer is regular vigorous exercise. I feel that I must have a different type of PD or something than most of you have because there is no way I can do any vigorous exercise. Please don't tell me to try...God knows I have...and I have never been a sedentary person. Now when I start exerting myself doing anything I feel more ill and shaky and just feel like I'm going to collapse and it keeps getting worse.

  • Parkinson's related fatigue can be disabling and will clobber even the most motivated.

    That said, your experience seems different that what I know of PD fatigue. IIRC you are taking some psych meds in addition to your PD meds. Your symptoms may be a result of the interaction of the psych meds with the PD or the PD meds. If so you would not be the first person on this board to have had adverse effects from such medications.

  • If you can afford it get a Theracycle. Use it at level 15 for 50 minutes twice a week and it will help your symptoms a lot and it is easy. Pretty much anyone can use it. It is a bit expensive but it works to relieve fatigue in a big way. I think it lessens fatigue by as much as 70-90%.

    Also, take melatonin, 3 mg at night before you go to bed. It is an extremely powerful brain antioxidant which quenches the free radicals in the brain caused by breathing as this may be the possible initial cause of pd. It should help slow the disease down.

  • Please keep on taking the Melatonin. Don't see the results right away it must take time for your body to adjust and the Melatonin to build-up in your body. It has made a big difference in the amount of sleep I get.

  • Beckey. As I was reading your post, Scott, the lawyer you referred to, was being interviewed on the news! He stated that he was diagnosed 17 years ago & he looked great. He said some additional symptoms come up periodically but he's doing better overall and is still able to practice law. He was our county prosecutor years ago & at that time had to use special equipment to type (voice activated sofware). Now he is doing so much better. What an inspiration!

  • I'm so glad to hear it! I wish I'd seen the interview.

  • Hi, Beckey, Rock Steady Boxing has been a Godsend for my guy! He was diagnosed with PD less than a year ago but his symptoms are Cognitive primarily, and RSB was introduced at our YMCA a few months ago. For all who are interested, here's a link: rocksteadyboxing.org

  • This is just my opinion from experimenting over the years, but I believe you can slow the progression by consistently doing a certain type of exercise (one that pushes you to your limit plus a little more, like the non-contact boxing) and taking lots of antioxidants and trying to stay away from stress as much as possible ( meditation &/or deep breathing). These things don't stop the disease because whatever is damaged is damaged. It will still progress at a slower rate until we know exactly what it is that damages those cells. Kind of like a car needing oil. If you do nothing, you're not going to be able to go any longer. If you treat your body good & give it the things it needs, it will keep going for awhile longer, but it still won't last forever. The person that doesn't put oil in his car will run down a lot faster. Exercise, antioxidants & some supplements help keep any of the good cells that are left from deteriorating as fast.

  • Did you exercise before getting pd? I did, it may have prevented me getting it earlier, who knows? Seems so far we don't know why it can't be stopped, no matter what we do. It isn't a virus after all. So why when doing the things recommended does it not stop? If it can be slowed can't it be stopped?

  • Hi Osie. So many questions! As a Pd patient who has got appreciably better, and who has no professional mediacl training, my answers are as follows:

    1. Pd is chronic because there is no cure.

    2. Pd is degenerative because it continues to destroy more and more brain cells.

    3. Alpha synuclein is neing produced in the brain by the pd. Until scientists have found out how to stop that production it will continue toget worse.

    4. What can be done to either get rid of some of that alpha synuclein or produce more glial cells? What I have done is four different things: a) I walk as fast as I can for one hour, three times a week. b) I continually get rid of any unhealthy stress out of my life. c) I have adopted a positive attitude towards the treatment of my Pd. I don't depend on medication as none of it does anything to slow down the progression of my Pd. d) I keep my brain busy with Sudoku puzzles, cryptic crossword puzzles and computer work.

    All of this appears to help to either repair or replace my damaged brain cells.

    Until there is a cure for Pd I will continue to reverse my symtoms by doing what I do and Pd will continue to destroy my brain cells.

    I hope this all helps you!

  • In familial PD there is an over production of alpha synuclein, for others research is not clear (could be the same) and it is unclear why it clumps. You are in the regeneration camp - cells can be reproduced/reactivated faster than those being damaged.

    Maybe it is a bit like cancer cells misfolding and once it starts it is hard to stop?

  • Hi Ozie. I am not sure that familial Pd is any different to other Pd.

    I understand that there has to be a genetic disposition in everybody in order for them to get Pd. It stands to reason that if anybody has the necessary genes for Pd to take hold, it does not mean that my chldren will have Pd, because there appears to be some other factor, other than toxins that needs to be present, that is already present in the familial Pd cases.

    It's a mystery!

  • go to the clinicrowd mannitol ..page it is being reversed by mannitol repairing the damage...

    also i have had good results giving back the toxins that cause the neurological damage in the first place...as a pattern ie homeopathically ..when we stop using pesticides and organophosates the number of cases will go down lookat stephenie seneff s work on youtube ....for more info

  • John

    Your msgs are consistent and my integration of them has helped me eliminate almost all of the 10 or so symptoms that I had when I was diagnosed as having a mild stage of PD 10 months ago.

    I am hoping that two current large-scale medical trials -- focusing on Inosine and NAC -- will pan out. In the meantime I am taking high doses of both.

    Inosine raises urate level, which is supposed to be neuroprotective. I take 3G per day. It should be chased with Potassium Citrate to min risk of gout and stones.

    NAC is thought to generate dopamine, but I am less certain about this process. I take 4 capsules per day.

    I also consume 1200mg of CoQ10 per day at the suggestion of a senior neurologist at Mayo, who also prescribed 10,000 steps per day, which I frequently gauge with a FitBit.

    I am still fully productive. Often have to discipline myself away from my work, which I used to think was a strength. But if I do work nonstop one day, I feel less energized the next until I have exercised.

    (I'm not sure what the always positive effect of ex is on PD symptoms, but I do find it curious that the rival hypothesis of its endorphin effect is never mentioned in the PD literature.)

    And as you have suggested, I try to avoid stress when possible to avoid my sometimes "hair trigger" response.

    Hope some of this is useful.

    Bob Miles

  • It seems that research is almost clueless about a way forward.

  • I was dx 11 years ago and finding the right thing to do for your pd can take a long time. It took me 9 years to find mine. My first two DRs meant well but were poorly informed about Pd. My recovery began with a new DR and starting C/L (carbidopa levodopa). I have taken it in many doses and several types. Today i take 6 50/200 ext release and 6 25/100 a day (2.5 times more than recommended dose for a 24 hour period) and 1 6mg Requip 24 hour release a day. I have suffered many side effects some so terrifying i went to the er 3 times. 2 times after i starting taking C/L. But i never stopped taking C/L. After learning what was side effects and what was pd i just began to ride out the side effects and keep trying smaller and larger doses. Until the dose I am now taking. The side effects became less and less over time. Now i have very few mostly at night.

    As for slowing PD down there is no way of measuring it. It runs a different rate for everyone and at different rates at different times for many. As for stopping it that is the same as a cure time will tell that one.

    I do not believe i have slowed or stopped my pd. I use the word control. I control my pd almost completely.

    In my opinion we can not control our pd with only meds or only exercise it takes both.

    John says

    "I don't depend on medication as none of it does anything to slow down the progression of my pd"

    This statement (to me) demonizes meds. Encouraging someone not to take meds is not the right thing to do. We should just relate what we do and how it helps us and let everyone find what works for them.

    Doing CrossFit does more than help control my pd it gives me something to look forward to every day and helps to make time pass faster. It makes me stronger fast and better able to take on what ever life throws at me.

  • Whilst there is a lot of money going into research I think a lot is being duplicated and money being wasted.I an taking part in several research projects and a lot of the tests ,evaluations ,and questionnaires are basically the same.WASTE. If basic data was taken and then shared a lot less time and money would be wasted on duplication.

    So much of it is just box ticking ,cognitive tests rarely hands on assessment.sometimes I think it's about getting papers published to enhance careers and gain brownie points.

  • I agree!

  • What a negative view!

  • Link to info


    Not being negative just realistic.My wife's a nurse and sees it first hand not just PD research but a lot of other research.

    A crucial clinical trial of the most promising new treatment for Parkinson’s disease in decades might be delayed because of a feud between a key scientist and the influential Michael J. Fox


    The episode also highlights the tension between scientists and foundations that are no longer content simply to dole out money. Following the lead of the colossal Bill & Melinda Gates Foundation, major medical research philanthropies increasingly seek to coordinate or manage studies, or control details of how they are done — vexing many grant recipients.

    In the above case, the clash involves nilotinib, a cancer drug tested by scientist Moussa and his colleagues in 12 Parkinson’s patients — many of whom described substantial relief from symptoms such as shuffling gait and cognitive decline. Although the trial was small, the results announced last year thrilled doctors and patients who have waited decades for a glimmer of success.

    Discussions between the sides lasted about six months, during which Fox officials reviewed and asked for changes in the Georgetown study design. Moussa disagreed with some requests involving verification of concepts he said had been demonstrated in the initial study. The modifications would “delay us for one year, and this was not good for patients,” Moussa said.

  • Well headlines like that do get to sell papers.

  • That maybe but most of there articles address issues that rarely get seen by Joe public.

    Dr Charbel Moussa the Georgetown scientist Researching nilotinib forPD stated

    “We thought it was a scientific discussion, but (the foundation) had alternate motives,” Fox engaged in “a premeditated attempt to cut us out,” “Some people think they are the owners of the conversation, the owners of the scientific debate, the owners of Parkinson’s research.

    Leading a trial for the most important Parkinson’s treatment in more than 40 years could bring the Fox Foundation valuable cachet and more donations, according to executives of other philanthropies.

    I think it's scandalous that large organisationslike MJF think they can walk over an individual like scientist Dr Moussa for their own ends and the public should know about it

  • I read that getting research money is very difficult. so, even if something meanwhile has been done they will do it anyway.

  • Brownie points = $ funding = mortgage, food, clothes, shoesies on kiddies feetsies

  • yes as we know with any cancer research as we've seen over the decades --that generates BILLIONS - they deny any natural cure - in favor of pharmaceutical hocus pocus.

  • No treatment has been proved to slow, stop or reverse the damage done by Parkinson's disease (PD). Some drugs, such as nicotine and ibuprofen, have been observed to be associated with decreased risk for the onset of PD. Other possibly neuroprotective drugs include isradipine, which is prescribed to lower blood pressure, and simvastatin, which lowers bad cholesterol. Uric acid, a waste product that causes gout, has also been noted to be associated with lower risk for PD. Uric acid, isradipine and simvastatin are being tested in large clinical trials right now to see if they indeed do at least slow PD. No results have been reported yet. Azilect (rasagiline) was thought to be neuroprotective based on early studies, but the evidence was too weak to convince the FDA that it has any benefit aside from mere symptomatic relief, like the other PD meds. It is hard to study exercise in a double-blind placebo-controlled fashion, but moderate exercise seems to be beneficial in PD by universal assent, so there is not enough "equipoise" to ethically conduct a trial which would limit or prohibit the control group from exercising.

  • I should add that possibly neuroprotective ibuprofen and nicotine have not been tested in a double-blind placebo-controlled trial, which is necessary to prove benefit in slowing the underlying disease process. Both of these drugs, of course, have potentially harmful side-effects and should not be used to treat PD until they prove beneficial in PD.

  • There's M13 in clinical trial. It is promising.

  • I am surprised at the loss of physical strength and movement that happened to me so fast. I thought there would be more time but the rate of deterioration increased suddenly. I was put off my feet by a couple of health conditions unrelated that resulted in some surgery and rehabilitation over 18 months. The struggle to get back to a reasonable point that I can do much of anything is explained by the medical people who were helping me as a matter of time. I do not have time. I suggest that you do not waste your time worrying about a cure, believe me, you will know when they find one. Instead , go out and live ,laugh, love, and be happy. Enjoy yourself , it is later than you think.

  • Thank you Gymbag. I'm forever reading how I need to exercise but I just don't feel physically up to it. Just doing a little house work or a moderator pace 20 minute walk is about all the exercise I am capable of, and it wipes me out for the rest of the day. I get worn out quickly just by doing things like painting. I was a prolific painter but haven't produced anything since Oct. I too am very surprised how much worse I'm this year as compared to last. I fear the PD I have is progressing very rapidly and I don't honestly expect to "go long" with this disease.

    If your interested I have a lot of my paintings on this FB page facebook.com/PaintingsbyThe...

    None are for sale...they are either sold or I decided to keep them.

  • TheresaCurley You're pictures are amazing! I can't imagine having that kind of talent.

    What meds and supplements do you take? Something is zapping your energy & I wish we could figure it out. I know PD can bring on fatigue, but it sounds like you suffer a lot. I understand that exercise is not for everyone, but I try to encourage as many people as I can because I have personally seen so many people improve. People that have exercised prior to PD & others that have not ever exercised. Don't give up. I can tell you're a strong & determined person & you'll figure this out. Maybe a change in supplements, by experimenting a little, may help?

  • I just started B12 shots - totally helped me!

  • Was your b12 level low or did you just decide to try the shots

  • I have been getting B12 shots for over a year now. They use to help more than they do now.

  • I agree with laglag. You can figure it out. Something that probably is not PD is causing this--at least you can think that way--and you can get it under control. Plan meals ahead, easy but nutritious meals. Then make them when planned. Get your husband to get the groceries or go with you to buy them. My husband gets half the list and we get out of the grocery quickly. I have found lately that deciding on the groceries and finding them in the store stresses me. There are too many choices. I like knowing my husband is in the store too. Make lists and cross them out for household chores or other things that you need to do. I think you can do this.

  • You are incredibly gifted! I pray that your energy returns so you can bless us with more of your beautiful art. Do not give up!

  • You need to get back to your painting, it is wrong to not share such talent with the world.

  • Theresa, your artistic talents invite one to see the world with "new eyes". Thank you for sharing the beauty of your soul.

  • Great talent! I hope you can find the strength and energy to continue soon. TC.

  • Kind of you ma'am to share your FB page for us to view your paintings. Such beautiful images need to be shared, you are so talented.

  • You are a talented artist! It saddens me that you sense a rapid progression of your PD. Maybe a second opinion is in order. I'm personally pursuing alternative treatment. My mom is late stage (22+ years) and I am not going to follow her path. I'm frustrated that very little progress has been made in decades and in fact the death rate from PD has gone up. My mom had a stem cell transplant, this therapy has been shown to be ineffective. She had DBS and it has helped with her motor symptoms, but what has the pharmaceutical therapy cost her? My once brilliant mom can't complete a sentence, but I know she understands what I'm saying. I'm not her caregiver and do not make her medical decisions, my parents are from the generation where you don't question the wisdom of doctors. I will not consider a L-dopa/Carbidopa combination for treatment after reading this scientific research paper and seeing what my mom has endured. I hope this helps you in your journey.


  • Thanks for the link. Something about this article puzzles me. It says that the only value of carbidopa/benseraside is to minimise nausea? I thought its main role was to help the levadopa pass the blood brain barrier? There appears to be no mention of this in the paper.

    It is very scary if if c/b does deplete B6 and others. PWP if this is true are between a rock and a hard place. Without medication they are stuffed, with it they are stuffed. Is this building a case for mucuna?

  • Other things about the article by Marty Hinz raise suspicion. This is as a result of my training for 30 years as a researcher.

    The paper is "perspectives" not a rigorous research article and may not have been subject to peer review.

    The journal is new and open access and therefore not highly ranked or rigorous as many journals.

    The style of writing is unscientific and emotional in places - deliberately creating a storm.

    As mentioned above it doesn't stress the main role of carbidopa, surely this is a serious omission that calls into question the value of the paper.

    As mentioned elsewhere on this site, Hinz is selling his solution. I don't know much about this but if it was that good it would be in the top journals in the field.

  • I appreciate your comments! I found this information when looking for an integrative MD in my area. I believe the article was peer reviewed, and the authors do disclose their conflicts. In my opinion this information invites one to do their own independent investigation.

    It's interesting to me that a plant derivative supplies L-dopa, it's not a pharmaceutical so there isn't much motivation for them to pursue it. That doesn't mean we as individuals can't opt for other therapies. I'm speaking for myself having observed a 22+ year progression of my mother's PD with no effective treatment, AND no real investigation into causation.

    If you don't identify causation how can you ever hope to develop an effective treatment? The fact is there's big money to be made keeping people sick. And if causation is allowed to continue unabated there will be a steady stream of "customers" (patients) to feed the system.

    There's no financial incentive for change in the pharmaceutical industry, unless people stop buying what they're selling. I'm an organic farmer - the pharmaceutical industry and the agricultural chemical industry are using each others playbook.

  • Hi Gymbag, I am not worrying about a cure, I just want to know where current thinking is at.

  • The fact that Parkinson's symptoms are so different in each person seems to add to the problem of finding a way of slowing this degeneration. I belong to a support group. One lady takes Madopar and her symptoms are completely controlled. I take Madopar but it does not control this tremor in my hand which affects my quality of life. Have now joined a knitting group because knitting keeps the tremor under control and for a while I can escape from Parkinson's.

  • Healthy interaction. You all get "A"' for attitude which has already improved my morning. Chronic A yields better outcome. Thank you Ishbi-Benob!!!!

  • U da man

  • Who daman?

  • One of the posts above noted that exercise is helpful due probably to an endorphin effect but researchers never mention the endorphin effect. But in the sentence they wrote "ex" to abbreviate exercise and on 1st read I thought they were inferring that Ecstasy was of benefit and it was being ignored. When I realized they meant exercise my mind continued regardless on a tangent about getting high to enjoy life while there is still some life left in me. :)

  • Parkinson's is a (usually) acquired metabolic defect wherein cells become unable to break down and recycle the alpha-synuclein protein. As a result alpha-synulcein accumulates over time and interferes with cellular functions. This accumulation causes disease progression. It is deposited here an there in characteristic clumps called Lewy bodies after their discoverer.

  • Do we know why the cells become unable to break down and recycle the alpha-synuclein protein?

  • All of the links have not been established AFAIK. However, some of the pathology is understood. It is quite technical and deep in the magic of molecular signaling:


    "Increasing evidence suggests that the c-Abl protein tyrosine kinase could play a role in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. c-Abl has been shown to regulate the degradation of two proteins implicated in the pathogenesis of PD, parkin and α-synuclein (α-syn). The inhibition of parkin's neuroprotective functions is regulated by c-Abl-mediated phosphorylation of parkin. However, the molecular mechanisms by which c-Abl activity regulates α-syn toxicity and clearance remain unknown. Herein, using NMR spectroscopy, mass spectrometry, in vitro enzymatic assays and cell-based studies, we established that α-syn is a bona fide substrate for c-Abl. In vitro studies demonstrate that c-Abl directly interacts with α-syn and catalyzes its phosphorylation mainly at tyrosine 39 (pY39) and to a lesser extent at tyrosine 125 (pY125). Analysis of human brain tissues showed that pY39 α-syn is detected in the brains of healthy individuals and those with PD. However, only c-Abl protein levels were found to be upregulated in PD brains. Interestingly, nilotinib, a specific inhibitor of c-Abl kinase activity, induces α-syn protein degradation via the autophagy and proteasome pathways, whereas the overexpression of α-syn in the rat midbrains enhances c-Abl expression. Together, these data suggest that changes in c-Abl expression, activation and/or c-Abl-mediated phosphorylation of Y39 play a role in regulating α-syn clearance and contribute to the pathogenesis of PD."

  • lolz.

    I was just trying to answer Ozie's question as best I could.

    Translation of the quoted part: molecular messaging gets messed up inside the cell.

  • Patrick is smarter than the average bear

  • Ha! Humor is good for PD!

  • That is why different people have different symptoms cause it get deposited in different places in your brain that affect different actions made by your body.

  • Alpha-synuclein aggregation is a symptom; genetics play a role, some of us are deficient in PON1 detox pathways, called slow metabolizers and others (me) have a BChE deficiency; I believe the cause of all neurodegenerative diseases is exposure to environmental toxins - poisoning. Which one(s) is variable, at the top of the list is pesticides, primarily organophosphates (glyphosate i.e. Roundup).

    I'm new here and will put more on my page.

  • As the most common age of onset is between 50-60 it could indicate that it is exposure to toxins (in food, air) over a life time (50 years) and genetical inability in the detox pathways singles some out rather than others. Some people might have greater exposure to toxins but not be affected.

  • Somebody on here made a good point about people getting pd hundreds of years ago before modern day toxins?

  • "Toxins" have been in use for centuries; common neurotoxins include lead, mercury, arsenic, cyanide, manganese from metal working and others. The modern pesticide DDT (thought to be safer) replaced lead arsenate as an insecticide.

  • Pesticides indeed. Top of the list are pyrethroids which had been thought to be non-toxic to mammals .. except for a strong association between between pyrethroid exposure and Parkinson's. See here for more: tinyurl.com/zjrxe49

  • I get the distinct impression that the 'Establishment' is looking for a 'Chemical Cure' for Pd and are not interested in encouraging patients to do exercise. They keep talking about controlled double blind studies for various forms of exercise. It is not possible to do double blind studies!

    Why doesn't someone do a study on exercise with say 100 participants and see how many of them get better? If all of them improve, by varying degrees, it proves beyond doubt that exercise works. This can be taken one step further and do different studies on different forms of exercise and compare the results.

    Many more patients will do exercise if they know that the results have been studies and have proved to be successful and to what varying degrees.

    Right now, there are not many people throughout the world getting 'better'. If more and more patients did more and more exercise, there would be more patients getting better!

    Perhaps I have answered my own question! Who wants patients to get better?

  • Every neurologist I have seen has agreed that exercise is the best thing a PD patient can do for themselves. And I believe that is true. That doesn't change the fact that I'm not able to exercise much before collapsing and trying to slowly increase has just made matters worse. It is definitely a tool but not a panacea. It's not because I never exercised, I use to be very much into walking long walks everyday here in the country. Just can not do it any more and that's is what it is...no lecture please.

  • Nobody, but nobody wants to kill a cash cow.

  • Nobody other than the cowherd! Oh! The Cash Cow might have an opinion on this one.

  • k thought oarkinsins was caused by loss of dopamine and by the time we notice it have already lots about 70 % .

    If they don't find a drug to stop the progression it's bound to progress surely

  • The loss of dopamine is a result of damage to cells that produce it. The cells become damaged as a result of the protein alpha synuclein forming clumps that render the cells disfunctional. Why alpha synuclein forms clumps in pwp is the inability to clear it away - see park bears post above.

    So people are often taking anti-oxidants (NAC, COQ10, green/detox tea, etc) that have the capability to pass the blood brain barrier in the hope it will clear the clumps of alpha-synuclein.

    This is my simplistic understanding of it all. Hope this helps?

  • This is how it works. lifemedical.us/wp-content/u...

  • It's not going to suddenly stop is it.

  • No, that is the case. People seem to misinterpret my original post thinking I am saying we can stop PD. I wanted to know why it can't be stopped, scientifically, and whether progression can be slowed (see my post below on the term "slow progress". There are some knowledgeable people on this board who have a skill in explaining technical things simply so I was interested in what they might say. In addition, everyone with pd has a view on the topic and that is interesting also.

  • I guess there is general confusion over the term "slow the rate of progress" or degeneration in relation to pd. There are three interpretations of this.

    1) Slow the rate of loss of dopamine producing cells in the brain.

    2) Slow the manifestation of symptoms.

    3) Slow the rate of physical and mental decline.

    They are interrelated. For example, exercise may not influence 1 (or it might, who knows) but can influence 2 and 3.

  • Apart from anything If you are able aven the smallest amount of exercise helps anyone . It also lifts your mood .

    I worry when someone encourages you to do so much exercise when you are unable because it will make you feel better .

    Family who read that expect there loved ones to be able when they are not .

    It depresses them and their own family think they are giving in ,

    I considered my husband a very stoic man , he swam five weekdays all his life . Until he was no longer able or safe .

  • Beckey and JohnPepper and All Others: Beckey: You said you wish you could see the interview with Scott Newman, I found it on the website for Channel 8, one of our local news channels.

    John: Stephanie Combs-Miller did a study about RSB and other exercise programs. She talks about it in this interview.

    All Others: There are 4 parts to this interview, each a little over 2 minutes each, all are very informative. I would recommend everyone take 10 minutes and listen to this interview and it will help give you a view of what Rock Steady Boxing is all about and how and why it helps PwP's.


  • Why can PD be slowed but not stopped? I ask the same about death and aging - "doesn't make sense!".

  • Not really, pd is not simply ageing, it is a malfunction, so it is a valid question.

  • The "aging" that's going on with PD is oxidation (ROS-reactive oxygen species).

  • It's called auto-induction, which is a chemical chain reaction in the brain (domino effect). The question is what was the triggering event and how can it be interrupted.

  • This post generated a lot of responses so maybe I will try and summarise. Just why the alpha-synuclein can't be stopped from clumping and a-s cleared away is unclear, although we know that it is a defect pwp carry. Apart from things like very high exposure to chemicals on farms or in war zones most people don't really know what triggered it. This plus the inability to arrest pd is frustrating from a medical and personal point of view.

    It seems the jury is out on whether pd can be slowed, although it depends how you interpret "slowed" (see my post above). Cleary, pwp want hope in some form or another as without that pd can have a demoralising effect that can ironically impact more severely. So it is probably good to believe that something is helping because it helps you face the day better and get more out of it.

    It is not easy to sugar coat PD. There are probably worse things though although that may be little consolation.

    My assessment of health issues on a scale of 1-10:

    10) Terminal cancer, inoperable brain tumour

    9) Cancer that keeps coming back over a few years (and kills)

    8) Diabetes that requires limbs removing

    7) and 6) MS and PD - depending on severity and type

    Are there others that should come before pd?

  • First and foremost no two people re the same whatever they try

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