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Dr. Lowe, from In The Pipeline, wrote Parkinson's As An Autoimmune Disease: More Evidence:
For many complex diseases, you'll find that there are a couple of hypotheses floating around them that are hard to prove and hard to disprove: one is that they're actually caused by some (as yet unrecognized) infectious agent, and the other is that that they're actually an autoimmune/inflammatory disorder. You can also recognize that these two can have features in common, as seen in something like Guillian-Barré syndrome, where a (usually innocuous and often hardly noticed) viral infection or other stimulus can lead to a sudden autoimmune crisis. A whole list of conditions have had such explanations attached to them, more or less persuasively: Alzheimer's, obesity, various forms of arthritis (with little doubt on the autoimmune side), diabetes (Type I, certainly, but even Type II), multiple sclerosis, Parkinson's, and more. Those links lead mainly to autoimmune explanations, but infectious-agent hypotheses are found quite easily as well, and going back many years.
A new paper adds what might be strong evidence to the Parkinson's explanation. It's been known for some time that there's an association between the disease and MHC (major histocompatibility complex) alleles although (at the same time) having another autoimmune disease doesn't seem to raise the risk for Parkinson's itself. That's interesting, in that the brain has mostly been thought of as an "immunoprivileged" compartment, but it's also been increasingly clear that this doctrine is not as solid as it might be.
From the research article:
Approximately 40% of the participants with Parkinson's disease in our cohort exhibited immune responses to α-syn epitopes, and these responses may reflect variations in disease progression or environmental factors. The fraction of patients who display these responses in classic autoimmune disorders such as type-1 diabetes, rheumatoid arthritis and multiple sclerosis is often around 20–50%. As with type-1 diabetes, which features epitopes that are derived from both preproinsulin and additional proteins, it may be that epitopes related to Parkinson's disease are derived from α-syn and additional proteins.
In short, the researchers found that the immune system in patients with Parkinson's disease can recognize the protein associated with it and induce a response that will kill neurons. If Parkinson's disease is autoimmune, then current therapies for other autoimmune diseases may also be relevant for Parkinson's disease.
Research Article: https://www.nature.com/nature/journal/v546/n7660/full/nature22815.html
https://en.wikipedia.org/wiki/Parkinson%27s_disease
https://en.wikipedia.org/wiki/Autoimmune_disease
Previous discussion of Multiple Sclerosis treatment: https://soylentnews.org/article.pl?sid=16/06/13/1038232
(Score: 3, Informative) by ledow on Friday June 30 2017, @09:50AM (2 children)
They don't need to be that similar. The immune system isn't "intelligent", it doesn't go "recognising" things as you may have been told.
It just has an awful lot of things floating around that interlock with certain edges of certain molecular structures / cellular structures that neutralises their effect, or even "tags" them for removal by other parts of the immune system.
It could just be that an immune response present in the rest of the body in most people (e.g. almost everyone on the planet has a certain range of base infections ALL THE TIME) acts in the same manner as it normally would, but if it's allowed through the blood/brain barrier, and "latches onto" parts of brain cells that normally it wouldn't come into contact with, it causes problems.
I'm by no means medically-trained, but almost anthropomorphising the immune system is a mistake. The cells do what they do, and even the world's most advanced drugs work on the basis of "our molecule will lock into this other molecule if it happens to hit it in just the right way", which is usually enough - with the circulation of various bodily systems, random chance, etc. to mean that it significantly hits all the parts that it needs to hit often enough to "cure" you.
The brain is rather special in this regard as many mechanisms operate differently for it, but it could be a whole chain of weaknesses - a particular immune response to a completely different condition that happens to share a "molecular edge" with a part of a brain cell component, as well as a congenital weakness in recognition at the blood/brain barrier that lets it through, as well as a weakening or strengthening of the immune response in a particular individual generally, as well as a flaw in how the body replaces those lost / damaged cells, etc.
The immune system has no idea what is "hostile" or not. It just has a bunch of cells and chemicals constantly present that will - when they touch certain things - attach or destroy them, coupled with systems that increase the number of such cells (possibly based on how many are left in the blood after they've been attaching themselves to a newly-introduced infection), and a "cleanup crew" that's constantly killing things, and a feedback mechanism, and a way to stimulate production of more cells. It's not "confused"... it's doing whatever it has always done, but in a way that is slightly unique in all individuals and altered by circumstances (e.g. being allowed into the brain when it shouldn't be, or being exposed to a condition that molecularly "looks" a bit like a certain part of the brain from certain angles, or similar).
Chances are it will take DECADES to discover the exact link, with thousands of people studying it every single hour of the day, and even then it's unlikely to be the complete picture or allow an obvious cure (e.g. something that can stop the degeneration, without damaging "similar" cells that are useful, without hitting the immune system's response to anything similar, and some mechanism to replace that which was lost in the first place).
It could literally be anything, everything, or nothing that causes the problem. And focus is only just starting to shift from "these conditions just happen in some people" (and the same is being said of Alzhiemer's and other conditions, linking to diabetes and all sorts) to possibly suspecting a potential immune system link is present too. That might be the cause, it might be what stops it coming so rapidly (i.e. the patient is already pre-destined to get Parkinson's for genetic or other reasons, but the immune system keeps it at bay for most of their life), or it might be a purely incidental response.
Medical research is basically poking a big black box and trying to work out what's happening. For huge, symptomatic, serious conditions with obvious correlations, we do okay. For everything else, it's person-centuries of work. In humans, unfortunately, the black box is 60kg of the most advanced nano-scale technology, far beyond our understanding, coupled with a few billion years of evolution in the direction of "anything that worked at the time", that we've only been able to look at in any detail for 100 years or so, unique to every individual, that also happens to have a person's life attached to it which stops you playing about too much with it. It's a huge task, and headlines like this are really nothing more than thinking aloud.
(Score: 0) by Anonymous Coward on Friday June 30 2017, @12:04PM
I, Dr. Lowe
I r, ledow.
(Score: 2) by Joe on Friday June 30 2017, @03:44PM
While you are correct that the immune system isn't a conscious or intelligent entity, it is also inaccurate to portray it as random or undirected.
The immune system needs cell damage, "hostile" signals, and "foreign" molecules in order to mount a full response.
Dying cells release molecules that will attract immune cells and direct their path toward them by inducing nearby blood vessels to present attachment molecules for immune cells. Immune cells then recognize molecular patterns associated with "hostile" foreign entities (e.g. viral genomes and bacterial cell components) and secrete molecules to attract more immune cells and influence how they respond. T cells, that were selected for the ability to recognize "foreign" molecules, will then further direct specialized immune responses for the pathogen type (e.g. viruses, bacteria, and parasitic worms).
Immune responses that happen in the absence of any of those signals are due to a breakdown in immunological tolerance. An immense amount of resources are put into maintaining tolerance and there are several places (e.g. the CNS, eyes, reproductive organs) where the threshold for a full immune response is higher.
- Joe