NeuroTalk Support Groups - Explanation for why PD progression might accelerate during bouts of fever/infection?

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- - Explanation for why PD progression might accelerate during bouts of fever/infection? (https://www.neurotalk.org/parkinson-s-disease/246017-explanation-pd-progression-accelerate-bouts-fever-infection.html)

Tupelo3, I've read your response several times, but I just can't see how you came to understand my post in that way. I'll try to say the same thing once again, but this time in a different way.

From reference [4]: "While the activity of c-Abl is crucial for proper neuronal development, it appears that c-Abl remains relatively quiescent in healthy adult neurons, and there are few known functions of c-Abl in fully differentiated neurons. In recent years, it has been shown that activation of c-Abl in adult brain occurs in the context of human neurodegenerative disease."

From reference [2]: "c-Abl is a nonreceptor tyrosine kinase that is activated by oxidative and cellular stress"

Just from these two statements, it could be hypothesized that the inhibition of c-Abl might be a worthwhile thing to try.

I have simply outlined three different ways by which the inhibition of c-Abl might (hypothetically) result in protection of dopamine neurons.

Granted, hypotheses 1 & 3 have my name on them, but in each case I have only contributed the bit which says that c-Abl prevents Parkin from performing its normal function. The rest of hypothesis 1 and hypothesis 3 is straight from reference [1] and reference [3] respectively.

[1] Matheoud et al. (2016) Parkinson’s Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation, Cell 166, 314–327, doi: 10.1016/j.cell.2016.05.039.

[2] Brahmachari et al. (2016) Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration, J Clin Invest. doi: 10.1172/JCI85456.

[3] Yunjong et al. (2016) PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival, Cell Reports Volume 18, Issue 4, p918–932, doi: 10.1016/j.celrep.2016.12.090.

[4] Schlatterer et al. (2011) c-Abl in Neurodegenerative Disease, J Mol Neurosci. 2011 Nov; 45(3): 445–452, doi: 10.1007/s12031-011-9588-1.

I guess we'll just have to agree to disagree.

Quote:

Originally Posted by jeffreyn (Post 1239345)

A research paper from June 2016 [1] describes how, during bouts of fever or infection, the mitochondria within the dopamine neurons of a PWP could (attempt to) signal the immune system to kill the neuron.

Basically, the mitochondria release a specific protein, which is transported to the wall of the cell, where it acts as an antigen, signalling T cells to attack the neuron.

This process is normally prevented from occurring by the actions of the proteins Parkin and PINK1 (except in the case of those PWPs whose Parkin and/or PINK1 genes are defective).

Neuron Cell Death in Parkinson's May Be Caused by Overactive Immune System

However, as reported in another research paper [2], in (all?) PWPs the c-Abl enzyme interferes with the normal operation of Parkin.

[1] Matheoud et al. (2016) Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation, Cell 166, 314-327, doi: 10.1016/j.cell.2016.05.039.

[2] Brahmachari et al. (2016) Activation of tyrosine kinase c-Abl contributes to a-synuclein-induced neurodegeneration. J Clin Invest. doi: 10.1172/JCI85456.

Does anyone have personal experience of sensing that their PD has advanced noticeably after having a bout of fever or infection?

Also, can anyone point to where this topic has been discussed? I have a link which indicates that this is a topic of current research interest, but few details as yet.

slugmaniac comments on Scientists of Reddit, what's a phenomenon in your field that the average person hasn't heard of, that would blow their mind?

(I think the link came from a post/comment at HU)

It's funny how a post that didn't gain traction at the time can spawn such an interesting discussion months later. Thank you for the thoughtful post.

Tupelo3 said: "I guess we'll just have to agree to disagree."

Okay, let's do that for now.

It concerns me though, that I find myself disagreeing with you. I shall spend some time trying to deepen my understanding of this area.

Quote:

Originally Posted by jeffreyn (Post 1239538)

Jeff, what would be the fun in this if we all agreed on everything. As curem rightly said, this thread only got interesting when we debated an issue. That's how we all learn, particularly in a science where no one knows for sure what's right or wrong. I will tell you this, my disagreeing with someone's opinion in no way effects my respect for that opinion.

This whole thing was probably just a difference in semantic interpretation. Nevertheless, I would be happy to discuss this with you more off-line at anytime so we can educate each other ;)

Gary

I, too, seem to be germ proof. I haven't had a cold in years since being diagnosed and don't catch them even when everyone around me has a cold or flu.