Parkinson's Movement
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Alpha Synuclein: New Species is discovered called Pa-syn - could it be the cause of cell death in PD?

Alpha Synuclein: New Species is discovered called Pa-syn - could it be the cause of cell death in PD?

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?"

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:

4 Replies

"We showed that pα-syn* is made of trimmed α-synuclein resulting from a failed cellular attempt to degrade fibrillar α-synuclein aggregates. "

Good work - another piece of the puzzle put into place.

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I think so - I am hopeful about this


Good stuff.

So many questions still, such as why these proteins misfold, why aren't the chaperones and the proteasome (if I have that right) doing their job? Everyone has ASN, everyone has errors in folding proteins, why is it prevalent in Parkinsons? What makes PWP different?

Another piece in this puzzle:

"Lewy bodies are intracellular inclusions formed mainly by alpha-synuclein, a protein of unknown function that is present close to synaptic terminals; the oligomerization of this protein is considered a key event in the setup or development of the disease [31]. One of the reported copper-damaging mechanisms is the oligomerization of alpha-synuclein [32]; in fact, it is claimed by some authors that copper is highly efficient in producing the oligomerization of alpha-synuclein [33] and that this metal, and not iron, is selectively able to fibrillate alpha-synuclein [34]. That was also related to the ability of copper to cause oxidative damage because the alpha-synuclein oligomerization is linked to damage to the mitochondria and electron chain transfer."


Really interesting. Thx for posting.


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