Why do brain cells die in Parkinson's and what can we do about it video

[JayPwP]

Can someone make sense of this? 15:45 video time he speaks about a-syn

youtu.be/67XD7EbnKSU(Not working as expected?)?

[park_bear]

More detail about these alpha synuclein aggregates here:

healthunlocked.com/cure-par....

[Boscoejean in reply to park_bear]

Thank you Park Bear- I was trying to find if this guy had any published works since I started to read the transcripts of this video and I thought that it is incredibly long and wordy and when does the guy ever get to presenting any useful information. All these videos are incredibly frustrating. Like do you have to listen to them in the background while you are actually doing other productive work and hope you don't miss the part where anything helpful is said? I guess my patience level is not very good haha

[park_bear in reply to Boscoejean]

I agree. I have no patience for these one to two hour videos, and I think that is a good thing. Put it in a peer reviewed paper found via Google Scholar.

[OuttaIdeas]

I've watched the whole video. While there are some interesting bits about some of the things they're doing with induced pluripotent stem cells, and stratification of patient phenotypes so that more relevant patients end up in clinical trials targeted at the suspected cause of their particular Parkinson's, there isn't anything new regarding treatments or insights into the cause of disease that most patients haven't already heard.

It's more of a "we're still working really hard on it!" video.

[Fricnfrac1999 in reply to OuttaIdeas]

Thanks for laying it out for those of us that haven't had time to watch!

[JayPwP]

I thought maybe I missed something that someone else would pick up.

[peminc]

Apologies for not listening to the entire video, but my understanding is that PD has potentially several different neurotoxic pathways and triggers. However, it seems the medical community and this video present Lewy Bodies as a key identifying marker of the disease. These Lewy Bodies are comprised of alpha-synuclein and ubiquitin, which are proteins used in a variety of cellular processes from tagging proteins for garbage disposal in the case of ubiquitin, to what ever alpha-synuclein does. I understand AS is a protein that is found in various parts of the cell and involved in a variety of functions, including the process of transporting vessicles of dopamine (or many other proteins) to the synapse.

One theory is that some people with parkinson's make too much AS and it creates a bit of a traffic jam on the micro tubule highway. That would potentially cause the AS or other proteins to be tagged with ubiquitous for lysosome disposal.

To me, that's a reasonable explanation of one of the potential cell processes that result in cell death. There are probably other cell processes involved, including possibly those processes that support the mitochondreon. And it suggests the Lewy Body is not necessarily the cause of cell death but more about grave stone marker.

[mitochondria]

Hi Jay,

Since you got me curious :-), watched the video entirely. Sharing the takeaways from my point of view:

- Parkinson’s - 10% genetic/90% idiopathic (unknown cause)

- Oxford Studying 10% of Genetic population to understand Parkinson’s

- Whether protein aggregates (alpha-sinuclein/Lewy body) kills neurons or if that’s the last gasp of neuron trying to survive is unknown (my note 1* - Clinical researcher/neurologist/brain cancer expert Dr Matthew CL Phillips calls ‘lewy body’ fire truck - the presence of fire truck does not mean it caused the fire - link to his article below)

- Stem cells may be produced from adult skin cells and research underway to ‘differentiate’ them into dopaminergic neurons

- More than dopaminergic neurons are affected in Parkinson’s - two other types mentioned are cortical neurons and spiny projection neurons (my note 2** - link to Dr Matt’s article on ‘Parkinson’s impacts all neurons in the body’ below)

- mitochondrial/lysosome dysfunction in Parkinson’s

- Motor dominant/slow progressing Parkinson’s - may be more Mitochondrial dysfunction

- Fast progressing/Cognition issues type Parkinson’s - may be more driven by Lysosome dysfunction (my note 3*** - There are plenty of recent articles on Mitochondria-Lysosome cross-talk, Dr Martin Picard is world’s leading expert on mitochondria, his analogy is mitochondria is like a computer processor that talks to other organelles inside and outside cells including lysosomes).

Q/A starts at 51 mins, worth watching, first question starts with ‘Nettle tea’

My notes:

1* - metabolicneurologist.com/pe... - click on ‘Day 10 - The Lewy Body Enigma’

2** - metabolicneurologist.com/pe... - click on ‘Day 7 - A Disease Of Neurons, Not Brain’

3** - picardlab.org/publications.... - under 2023,

“Multifaceted mitochondria: Moving mitochondrial science beyond function and dysfunction”. Also checkout “Neurodegenerative disorders, metabolic icebergs, and mitohormesis” under 2024

Best.