Researchers in Japan have developed a technique to visualize how an abnormal protein accumulates in brains of PP patients

[Farooqji]

This is an important development

It has been known that a protein called alpha-synuclein builds up in the brains of people with Parkinson’s disease and Lewy body dementia, forming clumps called fibrils. But detecting these fibrils in living patients is difficult.

The researchers, including QST’s Hironobu Endo, developed a new drug called C05-05 that binds well to this protein. They injected the drug into eight healthy individuals, eight Parkinson’s disease patients and two patients with Lewy body dementia, and ran PET scans on them. The result showed that the alpha-synuclein protein was highly concentrated in the midbrain in the latter two groups.

In addition, the imaging technology showed that the more alpha-synuclein accumulated in the midbrain, the more severe the patients’ motor symptoms were. This means that the C05-05 could be used not only for diagnosis but also for monitoring the progression of the diseases.

japantimes.co.jp/news/2024/...

[jimcaster]

Interesting. I'd still like a definitive answer as to whether the accumulation of alpha synuclein is the cause or an effect of Parkinson's Disease. So many drug companies seem to assume it's a cause of PD and that simply removing it will be the silver bullet. I wish it were that simple, but I don't think it is.

[park_bear in reply to jimcaster]

There are about 20 different genetic mutations that affect alpha-synuclein one way or another and cause Parkinson's. This includes the A53T mutation that has been designed into a genetically engineered mouse that exhibits Parkinson's symptoms.

Mutations causing early onset Parkinson's

[jeffreyn in reply to park_bear]

PB, your explanation is incomplete, as it doesn't cover the cases of idiopathic/sporadic PD, and these are the majority of cases.

IIRC, regarding idiopathic/sporadic PD, one hypothesis says that something causes a-syn to become phosphorylated at serine 129, which results in the protein recycling machinery failing to deal with it properly. In this case then, the original cause is "something", and a-syn clumping is a downstream effect. It has yet to be determined whether cleaning out the a-syn clumps would be sufficient to set things right.

[mk2002wi in reply to jimcaster]

I hear your concerns about this. So, what is causing the protein build up?

[jimcaster in reply to mk2002wi]

Great question. I don't have the answer. I don't know if anyone does.

[Gioc]

Quote:

”In addition, the imaging technology showed that the more alpha-synuclein accumulated in the midbrain, the more severe the patients’ motor symptoms were. This means that the C05-05 could be used not only for diagnosis but also for monitoring the progression of the diseases.”

This is the coolest discovery I've ever heard and by the way it didn't cost much dollars at any foundation.

Let's try to get that stuff (asyn) out of our brains!

Thank you to share this  Farooqji , very interesting.

[LAJ12345 in reply to Gioc]

Except maybe the area is damaged and the stuff is sent to repair it or stop it deteriorating further. Like callouses to stop blisters.

[Gioc in reply to LAJ12345]

Hi  LAJ12345 , very acute observation as always.

Yes , this is also possible, but if I understood correctly, this drug binds to the alpha-synuclein composed in fibrils ( a compound form of asyn) and Lewy bodies, a fact that changes the context and validates once again the direct correlation between alpha-synuclein fibrils and Parkinson's disease symptoms.

I am not an expert on these things and I could be very wrong, but in my opinion being able to have an objective and precise examination of the progression of the disease will help research a lot.

scienceofparkinsons.com/alp...

cell.com/neuron/pdf/S0896-6...

[LAJ12345 in reply to Gioc]

Yes, it seems more for measuring and predicting than curing I think.

[LAJ12345]

that’s interesting. I thought the problem was in the substantia nigra.

From google

“The midbrain functions as a relay system, transmitting information necessary for vision and hearing. It also plays an important role in motor movement, pain, and the sleep/wake cycle. The midbrain, also called the mesencephalon, is a part of the central nervous system.”

What are the parts of the brain midbrain?

“There are three main parts of the midbrain - the colliculi, the tegmentum, and the cerebral peduncles. Of the 12 cranial nerves, two thread directly from the midbrain - the oculomotor and trochlear nerves, responsible for eye and eyelid movement.”

That explains why a wide variety of symptoms occur!

[Gioc]

link:

cell.com/neuron/pdf/S0896-6...

[MarionP]

I'm not so sure how important it is. Knowing this accumulation story, well when I was younger I seemed to think it mattered. But when you start thinking clearly, critically, it doesn't really help us a bunch does it. Oh it seems to feel good, until you start thinking. Knowing something about "how" didn't really help knowing what to do about it or being in the position TO do something about it. Of course I'm not in such a summer mood today.

[EdAllentown]

I checked the DNA report that I received from the PD GENE project at Indiana University. I don't have any of the gene modifications that they associate with Parkinson's.

I am also wondering about the emphasis only on DNA, sfter watching numerous YouTube videos by Dr Michael Levine.

His lab has been working on bioelectrity, the movement of ions across cell walls. He considers DNA "hardware" and bioelectrity "software".

He has been able to make changes in living creatures without touching the DNA using just bioelectrity. And the changes, like a 2 headed flat worm, stayed in the next generation.

See: youtu.be/XheAMrS8Q1c?si=oYd...(Not working as expected?)

as a starting point.

Ed

[peminc]

Very good & interesting stuff. Thanks!