Comment by themanualstates

Oh, I assure you that I don't trust my imagination on this!

Hence the disclaimer that it's super guessy what I wrote.

So I come to this perspective having had reason to look into synucleopathic disorders like Parkinson's and Lewy body dementia. Read a ton of literature as best I could. (Regular people can read academic literature. To actionable insight. It just takes some care regarding certainty, and one must work with doctors with anything significant. It's a… help the doctor help you thing.)

And indeed: Pesticides. That New York times article mentions paraquat.

It's interesting to look at how pesticides might bring about Parkinson's. Cell death in the substantia nigra.

It's interesting with paraquat that it's especially and specifically destructive to the lung. As well as generally-yet-specifically inducing oxidative stress, which seems as far as I can tell to kind of be… the cause of death so to speak?, for the crucial substantia nigra cells. The Wikipedia page on paraquat underpins this pulmonary impact reasonably well I think, well enough for the sake of discussion: https://en.wikipedia.org/wiki/Paraquat

Then there's stuff like this: "Elevated PM2.5 concentrations were significantly correlated with an increased risk of PD among patients with COPD. Furthermore, exposure to high PM2.5 levels can further increase the risk of PD." – Association between PM2.5 exposure and risk of Parkinson’s disease in individuals with chronic obstructive pulmonary disease in Taiwan: a nested case-control study, https://www.e-epih.org/journal/view.php?doi=10.4178/epih.e20...

And this: "This nationwide retrospective cohort study demonstrates that [Parkinson's disease] risk is significantly increased in patients with [chronic obstructive pulmonary disease] compared with those of the general population." — The association between chronic obstructive pulmonary disease and Parkinson's disease: a nationwide population-based retrospective cohort study, https://academic.oup.com/qjmed/article-abstract/108/1/39/158...

Then I've been surprised and sort of amazed to read studies of the OTC compound ambroxol in Parkinson's. These seem to show that ambroxol has protective effects against Parkinson's, even seemingly curbing the progression of the full clinical manifestation of the disease. Ambroxol is an over-the-counter mucolytic and "cough syrup" thing. It also happens to have specific antioxidant properties – redox-adjusting properties? – and in general very complex and very interesting effects on neuronal signaling; "Ambroxol is a potent inhibitor of the neuronal Na+ channels, explaining its anaesthetic effect", as per Wikipedia: https://en.wikipedia.org/wiki/Ambroxol

Ambroxol has extensive effects on fine pulmonary function "through several mechanisms, including breaking up phlegm, stimulating mucus production, and stimulating synthesis and release of surfactant by type II pneumocytes."

And! Get this: "Ambroxol is also anti-inflammatory, reducing redness in a sore throat. It reduces the release of inflammatory cytokines and histamines in cell cultures. It also acts as an antioxidant, scavenging free radicals and hypochloric acid generated by neutrophils.[14] These two effects explain its effect in treating acute lung injury caused by paraquat.[7]"

At that point I was like whoa.

Here's a bunch of research stuff on ambroxol and Parkinson's:

Ambroxol-induced rescue of defective glucocerebrosidase is associated with increased LIMP-2 and saposin C levels in GBA1 mutant Parkinson's disease cells – https://pubmed.ncbi.nlm.nih.gov/26094596/

Ambroxol as a Treatment for Parkinson Disease Dementia – https://jamanetwork.com/journals/jamaneurology/fullarticle/2...

Protocol of ASPro-PD: a phase 3 trial of ambroxol to slow progression in genetically stratified Parkinson’s disease – https://link.springer.com/article/10.1007/s00415-026-13683-7

Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson’s disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol – https://neurologyopen.bmj.com/content/5/2/e000535

Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations – https://jamanetwork.com/journals/jamaneurology/fullarticle/2...

It's wildly interesting. I'm super curious.

So a thing with these studies is that it's looks like ambroxol doses for Parkinson's need to be substantially higher than the cough-syrup/OTC-mucolytic doses. Seemingly to get enough to cross the blood-brain barrier. So this doesn't pin down any pulmonary foundation for Parkinson's.

But it is very, very interesting that... practically all of the stuff that impacts Parkinson's for better or worse always has a pulmonary element. All of it, as far as I can tell. But I don't know! I'm just seeing a structure of evidence as leaning a certain way. Could just be my imagination. And I don't trust it. But I'ma keep reading for sure.