OK, Here's my (simplistic) take away:
1. PD is caused by lack of dopamine. In PD brain autopsies, we often see Lewy bodies.
2. Lewy bodies are at least largely made up of protein, but a misfolded protein, called alpha synuclein (ASN). Because it is misfolded, it does not transfer signals between neurons properly.
3. Removing the ASN clumps *might* help halt the progression of PD, hence the clinical trials emerging, like PASADENA.
Some questions around Lewy bodies were presented in the blog "Are Lewy bodies fake news?" scienceofparkinsons.com/201...
It discusses the idea that there are different types of ASN and cites other findings that support this, "dopamine cells may be dying before Lewy bodies even have a chance to form, which would suggest that the presence of Lewy bodies does not predispose a neuron to cell death." Begging the question: Are these ASN clumps the cause of PD or a response to cell death in PD? So, If ASN clumping is not causing neuron death (which causes loss of dopamine which causes PD) then what does?
Then, "Alpha Synuclein: New Species" was just posted:
It includes the announcement that two Florida researchers had identified an all new species of alpha synuclein that they have called “P-alpha-syn-star” or Pα-syn* (that I posted a few days ago). Pa-syn appears to be a mini clump of protein inside the larger alpha synuclein clump inside the lewy body (again my simplistic understanding) and these Pa-syn are like toxic missiles seeking mitochondria then destroying them. Could this be the real culprit behind PD?
This seems to open an important door and stir a lot of additional questions. I am excited to hear more. What do you think?
More info: pnas.org/content/early/2018...