Video may Explain how too much dopamine could cause PD

[robinson621]

youtube.com/watch?v=Uap1kzI...(Not working as expected?)

[park_bear]

When I asked Dr Jonathan Sackner-Bernstein for his explanation of how it was possible for genetic mutations affecting alpha synuclein to cause Parkinson's he had no reply

[MarkPrana in reply to park_bear]

I'm still learning around this Park_bear.

Am I right in thinking the Pink gene mutation causes mitochondrial malfunction, which may lead to alpha synuclein misfolding/PD. And the GBA gene mutation may cause liposomal/autophagy issues that may lead to alpha synuclein misfolding/PD?

I'm trying to understand if Dr Jonathan Sackner-Bernstein's a interpretation could be compatible with some of the genetic variants.

Or alternatively, maybe not compatible.

It's a complicated field we PwP live in.

[park_bear in reply to MarkPrana]

Here is a list of mutations directly affecting the alpha-synuclein structure and that cause young onset Parkinson's

reference: molecularneurodegeneration....

Mutations affecting alpha-synuclein structure

[MarkPrana in reply to park_bear]

Thank park_bear, a lot to digest in there.

Am I right in thinking the SNCA gene mutations are distinct from PINK and GBA-gene mutations (and LRRK2, which is the other one I've read about).

So, what we have is 6 x genetic mutations that affect the SNCA gene, which affects aloha-synuclein production function directly.

This would be different to the others (PINK/GBA/LRRK2, etc.), which act indirectly on alpha syneclein via other mechanisms such as impaired mitochondrial function/autophagy/etc.

Please feel free to correct my interpretation, as my understanding is very much still emerging around all this.

[park_bear in reply to MarkPrana]

I believe what you have said is correct.

In my opinion, Dr Jonathan Sackner-Bernstein's theory may apply to downstream effects of Parkinson's disease, but does not address causation.

[park_bear in reply to MarkPrana]

My takeaway from all of this is that the alpha synuclein system is complex and precariously balanced such that any perturbation results in malfunction - what we know as Parkinson's disease. In addition to the above, this includes mutations that increase the amount of normal alpha synuclein, as well as mutations that affect the ability of the microglia to clean up excess alpha synuclein in the intercellular space.

[gomelgo]

I'm not sure I see how him having no answer to the genetics question negates his theory. Would you be willing to describe it to me as if I were a child? I get very lost in all the jargon.

[psyche100]

I wonder if his theory is contradicted by evidence that levodopa does not worsen progression such as this study: pubmed.ncbi.nlm.nih.gov/250...