Hypoxia Sensing and Responses in Parkinson’s Disease, 2024, Johannes Burtscher et al

Abstract
Parkinson's disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks of PD, including mitochondrial dysfunction, dopaminergic vulnerability, and alpha-synuclein-related pathology, and highlight the link with cellular and systemic oxygen sensing. We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD. Finally, we provide examples of preclinical and clinical research substantiating this potential.

https://www.mdpi.com/1422-0067/25/3/1759

 

There seems to be many similarities between Parkinson's and ME/CFS

Does ME/CFS which manifests with more cognitive impact share pathways ? Or genetic expression ?

To what degree is there overlap on physical symptoms ?

Is there a correlation between any Parkinsonian correlations and severity , or type of onset in ME / CFS. Given the link with viral infection and Parkinson's this may be interesting.

Could ME/CFS be a comparator arm in Parkinson's research - or indeed other research based on common correlations?

Other conditions such as Parkinson's benefit from better disease load research funding ( and public understanding) and drug development.

How do we widen research collaboration to be able to both raise ME/ CFS profile and benefit from a wider research based community ....

 

To me Parkinson’s and ME also seem completely different and don’t share notable similarities apart from the natural overlap that many diseases have (obviously the one is a degenerative and deadly codnition whilst the other one isn't).

I do think though that the Michael J. Fox Foundation For Parkinson’s Research, who are the largest funder of Parkinsons research worldwide and supposedly fund more research than the NIH, do some things that would be worthy of emulation for some similar groups in the ME and/or LC field.

Some of the things I think that are worthy of emulation in the ME and/or LC field and that don’t cost (too much) additional funding or resources would be:

• The Fox Trial Finder (https://en.wikipedia.org/wiki/Fox_Trial_Finder) is something that seems worthy of something analogue for LC/ME
• The foundation is very big on open data/resources and have set up large data sets that are easily accessible to everybody. They also have large collaborative programs. Perhaps one could copy some ideas from these set-ups? Their research tools program also seems interesting, but I don’t see how that could be applied to ME and/or LC

Another thing they seem to be very big on is cross-pollination from research from related diseases (Lewy Body Dementia, Multiple System Atrophy, Progressive Supranuclear Palsy, etc.). I 100% think that the patient organisations that only have extremely limited funding means, usually from patients, such as the OMF or Polybio should be fully focussed on ME and/or LC and shouldn’t be spending any money or resources on other diseases that anyways typically receive more funding.

However, I do think that a lot of clues could be uncovered from related conditions if someone like RECOVER would devote some very few resources to that instead of doing vague epidemiological questionnaires (the obvious problem is of course that these have been historically neglected as well).

• For those interested in EBV and autoimmunity does possibly MS hold vital clues or can we get some MS researchers interested in ME and/or LC or motivate these to include some ME and/or LC arms in their research?
• Does GWI hold clues to things in the nervous system we have no idea about and can that further or understanding of such problems in ME and/or LC?
• Does post-Ebola hold answers for viral persistence? Can symptomology and immune response be tied to a disease with a similar profile where viral reservoirs have been proven to exist and can post-Ebola serve as a testing ground to test methods currently being employed in ME and/or LC when trying to uncover viral reservoirs (for example can symptomology and viral reservoirs be tied to results of the Simoa assay in post-Ebola)? Can collaborations between post-Ebola and viral persistence researchers be established?

At least I don’t see how this would necessarily be less fruitful than exploring similarly ominous symptoms such as MCAS or SFN.

Other than that there were some very vague reports of α-synuclein in relation to Covid/LC and those researchers might be able to obtain funding for their research via the Michael J. Fox Foundation (I think Dysautonomia International are currently funding some of these projects and might at least benefit from a collaboration).

 

I found quite a bit of symptom overlap between father in law and daughter , perhaps though some are common to energy limiting conditions , perhaps he was atypical , or my daughter is, or both.
Not having a body related science background could of course mean I am barking up the wrong tree....

Aspects shared
Cognitive fog, can manifest as dementia like and is scary. This is noticeable for my daughter in a downturn.
Perception of time and " lost time"
Blurring of sleep and reality ( usually when in pem)
Sleep cycle disruption
Gait when tired
Proprioception issues - may be linked to vision when very tired
Internal tremor
Internal bone coldness
Muscle cramps
Numbness periodically
Shooting pain
Exhaustion ( my father in law made it clear tiredness did not describe how he felt)
Feeling of not enough oxygen in brain .

Hypoxia could underlie many symptoms , upsetting balances , triggering ROS, affecting signalling and mitochondrial function.

It's interesting also as some elsewhere with ME respond to dopamine modulators . There used to be discussions on the other place .

I agree that there should be much more collaboration and data sharing across groups who share symptoms / potential mechanisms

Apologies for lack of text formatting. My phone is playing up tonight