It could be people using mobile phones to read with their consequent blue light exposure.
I had a small look at MS and the myelin production thing could be an mtDNA/Splicing issue.
I have done a blog post about this:
Here is O3’s analysis:
Bottom line
The case for aberrant splicing in myelin production as a contributor to MS is biologically plausible and experimentally supported, but the case against it being the primary cause remains strong.
At present, the weight of population genetics and virology favours a model in which immune dysregulation (often EBV-driven) comes first, with myelin-splice errors acting as modifiers or amplifiers rather than root causes. Future high-resolution genomics and antigen-presentation studies will be needed to settle whether a distinct “spliceopathy” endotype of MS truly exists.
In the end the easiest way of finding out if splicing is the issue is to treat it as a splicing issue and see if that fixes it. After all most of the interventions are generally good for health regardless.
Yes, aberrant splicing can mis-fold SOD1 and even present clinically with Parkinsonism—but so far this looks like a medical curiosity, not the rule.
In mainstream idiopathic PD, all available evidence points to metal-binding and other post-translational disturbances, not splicing, as the proximate cause of SOD1 mis-folding.
That balance of evidence should guide both mechanistic thinking and therapeutic prioritisation.
Whichever way, however, SOD1 errors will cause further mitochondrial damage.
Yes: mice, and “PD-like”. That’s obviously limitations.
But from the paper I posted:
“We evaluated whether the blood-brain-barrier-permeable copper delivery drug, CuATSM, attenuated the misfolding and deposition of wild-type disSOD1 and associated neuron death in a novel mouse model that expresses this pathology.”
The paper you posted refers to dietary intake of copper. These may not be the same effect, quite apart from the form or delivery mechanism - this might also be an effect of administering a bolus to affect the relevant tissue. In other words, very different from dietary intake effects. YMMV.
[!]HEAVY CAVEATS[!]: imrpress India study; in mice; MPTP-induced PD.
Telmisartan Protects Mitochondrial Function, Gait, and Neuronal Apoptosis by Activating the Akt/GSK3β/PGC1α Pathway in an MPTP-Induced Mouse Model of Parkinson’s Disease
The study included 14,289 individuals with PD (mean age 72 at diagnosis, 59% male) and identified 23 drugs associated with reduced mortality risk at 8 years. These drugs included ranitidine (histamine-2 blocker); pantoprazole and esomeprazole (proton pump inhibitors); losartan (angiotensin receptor blocker); atorvastatin (for high cholesterol); tadalafil (for erectile dysfunction); levothyroxine sodium (thyroid hormone); phenoxymethylpenicillin, erythromycin, and azithromycin (antibiotics); 4 nonsteroidal anti-inflammatory drugs; combined codeine/paracetamol and tramadol (opioid analgesics); zopiclone and melatonin (sleep aids); mianserin (antidepressant); mometasone (nasal corticosteroid); 2 opium-derived cough medicines; and dexamethasone (ophthalmologic corticosteroid).
The four NSAIDs are piroxicam, meloxicam, naproxen, and glucosamin and the two cough medicines are ethylmorphine with and without a combined expectorant.
Our study also has some limitations. We did not have access to clinical progression scores or causes of death and, therefore, relied on all-cause mortality risk as an indicator of disease progression. Consequently, some of the results may not reflect disease modification but rather effects on general mortality, which we explored in the general population. Because aging is the strongest risk factor of PD, some pathophysiologic processes may be common to both PD and aging. This overlap may explain the observed associations in both populations, although most showed stronger effect sizes in the PD population. It is possible that drugs that displayed equally strong or a stronger association with mortality in the general population compared with the PD population do not have a PD-specific effect.
Among the identified drugs were macrolides, opioids, and melatonin, all of which have been demonstrated to influence mitochondrial quality-control mechanisms, which are central to the suggested pathologic origins of PD, but also to aging in general
The adjusted mortality curves for the drugs with a more pronounced association with mortality in the PD population compared with the general population are displayed in Figure 2. The adjusted mortality curves for the drugs with similar or larger effect sizes in the general population are displayed in eFigure 3.
For almost all the 13 compounds displayed in Figure 2 in the article by Tuominen et al., the eight-year adjusted mortality curves for people with PD and healthy controls diverged and had different slopes, suggesting that these compounds may have a disease-modifying role.
It’s a Norwegian paper. In Norway, melatonin doses below 1 mg are OTC supplements while doses of 1 mg or more are Rx drugs. The paper looked at “prescription drugs” so at least 1 mg of melatonin. It seems that they don’t have more than 10 mg: Medisin - Felleskatalogen
Great find! Had to clue levothyroxine (T4 thyroid) would do this well. Along with four opioid derivatives.
A few questions
-Any idea on the glucosamine dosage?
-Do you think chondroitin would be of any benefit? (as I’ve been using a combo supplement of glucosamine and chondroitin, but considering to go to glucosamine only next buy.)
-Is there a list of the other antidepressants they tested?
“Mianserin, the only antidepressant associated with reduced mortality in our study, distinguishes itself from other antidepressants by effectively and selectively elevating norepinephrine levels by both blocking its reuptake and stimulating its release.”
I wonder if other norephinephrine reuptake inhibitors would do well. Or other medications that stimulate its release.
Or if it could also be due to histamine blocking (H1 mostly) for Mianserin, since ranitidine was in the list (histamine-2 blocker). Meclizine did good in the ITP study, and it’s H1 blocker. It might have been the only histamine antagonist medication they have tested IIRC.
Check the Norwegian drug database (link above) and see which doses are sold there.
I have no idea what these drugs are sorry.
“We applied the emulated target trial framework and conducted a high-throughput, hypothesis-free screen of all drugs on the Norwegian market initiated by individuals after the diagnosis of PD.”
Thanks for the links above, I missed them earlier.
It appears the glucosamine is 400mg pills. It says to take 1 pill 3 times a day, or all 3 pills at one time.
1200mg total.
It also showed a glucosamine/chondroitin/msm (500mg/400/100) pill.
Interesting post about the beta-blockers.
Edit: Was late at night for me.
The glucosamine pharmaceutical appears to be a 1500mg pill.
Seems interesting the connection between nitric oxide and longevity: Tadalafil, ARB, Statin.
Citrulline malate or AAKG (arginine) might be a good addition for nitric oxide and mitochondria (citric acid cycle).
