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.

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.

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.