The villain in the head

Often I was already in the situation to try to explain to my fellow beings – and also to try to understand myself – what kind of illness MSA actually is? Why is it incurable, where does it come from and why is the trigger unknown? Man lands on the moon, the human genome is as good as decoded, there is a cure for AIDS and Ebola – so where is the problem?

I understand relatively well what is happening in my body (head), but how do I explain this in a nutshell? Most people think anyway that it consists of what you “can see”. So “a little walking weakness” coupled with “a little speech difficulties”. That there are a lot of other things that come along with this, and that all this is incredibly exhausting, up to the point of breathlessness and fainting, that’s something few people know. At least that’s how it is “at an earlier stage”, later when you are in a wheelchair or bed bound, you see and notice more, only until then most of your friends and family members have disappeared and don’t see it – but that’s a different matter.

So, the disease is in the head, something happens to the brain. But what?

No matter where or what I look up, I always end up with Alpha-Synuclein. Alpha-Synuclein? What’s that? Do healthy people have this stuff? What’s wrong with this Alpha-Synuclein? And where do I find an explanation that isn’t written for medical people and I understand?

Alpha-synuclein is a protein that regulates dopamine release, among other things. It’s a transport protein. Mutations in the Alpha-Synuclein gene are responsible for synucleinopathies, which are represented by many other neurodegenerative diseases, such as MSA.

In the brain, Alpha-Synuclein is mainly found at the tips of the neurons, in the so-called “presynaptic terminals”. The presynaptic terminals release chemical messengers, the so-called neurotransmitters. The release of neurotransmitters relays signals between the neurons and is crucial for normal brain function.

Yes, that means Alpha-Synuclein also has healthy people and it has a healthy function. Alpha-Synuclein is a normal component of nerve cells. Unfortunately, its function is not fully understood yet. In our case it goes a bit crazy and doesn’t behave as it should. We know that abnormal deposition and misfolded α-Synuclein (the protein chains become longer and longer and finally the characteristic protein clumps builds) is the reason for our disease. α-Synuclein is present in abundance in the brain, while smaller amounts are also found in the heart, muscles and other tissues. It can pass from the stomach to the brain via the vagus nerve. However, the detection of Alpha-Synuclein in the intestine does not support the hypothesis, that the protein is also able to travel in the other direction. Animal studies from 2016 show this, but this is only a guess so far.

The degeneration of the substantia nigra (an area of the brain) leads to Parkinson-like symptoms, that of the striatum (also an area of the brain) to the loss of dopamine receptors, which in the later stages of the disease leads to a loss of response to dopaminergic therapy.

Ataxia (a disorder of movement coordination in the legs but also in all other parts of the body) is caused by atrophy of the cerebellum, often together with atrophy of the olives and the bridge (both regions of the brain).

A loss of certain neurons in the spinal cord is responsible for autonomic dysfunction (a condition, in which the autonomic nervous system does not function properly. This can affect the function of the heart, bladder, intestines, sweat glands, pupils, blood vessels, etc.).

α-Synuclein is in any case the cause of neuronal cell death which in turn causes our disease. This is already certain. The amount of stored protein becomes more and more in the brain – how slowly or quickly this happens, varies from patient to patient, in any case always much too quickly actually – but this process is responsible for the progress of the disease. The reason for this abnormal drowning in the many α-Synuclein, and thus our abilities become less, our symptoms more and more severe. What is really going on in the brain, we know when we do a post mortem autopsy of the brain – a tissue sample, as with other organs, is unfortunately not possible in the brain – if the patient is supposed to survive the operation.

Once we know, why this abnormal deposition happens, what the trigger is, then we are one step closer to a drug. It is also difficult to find an explanation, that explains it in a language that is not too scientific and does not go into too much detail. I hope I didn’t say anything wrong. If you disagree, please correct me.

Where I have tried to explain it all in a nutshell, I have come to the conclusion that it is not possible to explain it in such a nutshell. It’s a pretty complex story. Trying to explain flu viruses doesn’t make it any shorter.

Researched from the following pages:
aerzteblatt.de
wikipedia,org
sciencemediacenter.de
chemie.de
genengnews.com

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