@medaura, thanks, from this article: “Nearly every scientist interviewed for this story does a few simple things. They filter their water, they run an air purifier, they don’t microwave plastic”
@John_Hemming on melatonin and PD (Chinese preprint): Regulation of mitochondrial dynamics and function by melatonin type 1 receptor in parkinson’s disease 2025
interesting…my father was an avid golfer and developed Parkinsons
This is quite probably one of the easiest things we do 3 to 4 times a week.
tVNS with a simple setup works. $100 and have the most flexible tVNS system on the market.
In conclusion, multiple lines of evidence call into question the iron overload hypothesis in PD pathology. If we consider instead that cells in humans with PD may be suffering from a functional iron deficiency (4), much more of the available data make sense. Epidemiological studies link systemic anemia and recent blood donations to higher PD risk (29). TH function and mitochondrial respiration both rely on iron; thus, functional iron deficiency will lead to decreases in dopamine tone and loss of mitochondrial respiration (which ultimately will drive cell death), both of which are hallmarks of PD. Iron removal via chelation only exacerbates these problems, particularly in drug-naive patients where excess l-DOPA is not on board to mask a decline (1, 2). Iron therapy, in RLS and in PD, benefits patients (9, 10). Removing iron in brains of patients with PD via chelation has been sufficiently tested clinically, with negative effects on patient outcomes. We should now consider the alternative hypothesis of functional iron deficiency and how we might tackle it therapeutically.
They’ll have to explain why anemia is protective in PD: https://www.cell.com/heliyon/fulltext/S2405-8440(24)10889-4
And why an iron chelator recently succeeded a PD like condition (MSA).
Gemini explains these paradoxes by saying:
So fixing failed iron metabolism might be the solution. Gemini says Ambroxol might help as well.
I think the problem is that neurons that are part of a neurodegenerative diseases as in are in themselves starting to fail and failing will fail in a number of different ways. What needs to be identified is the initial cause of the failure rather than the different ways in which they fail.
Mitochondria are highly dynamic organelles with complex structural features that perform several essential cellular functions, including energy production by oxidative phosphorylation, regulation of calcium and lipid homeostasis, and control of programmed cell death. Given their critical role, alterations in mitochondrial biology can lead to neuronal dysfunction and death. Defects in mitochondrial respiration, especially in oxidative energy production, have long been thought to be implicated in the etiology and pathogenesis of Parkinson’s disease. However, given the multifaceted roles of mitochondria in health and diseases, the putative role of mitochondria in Parkinson’s disease likely extends well beyond defective respiration. As such, mitochondrial dysfunction represents a promising target for disease-modifying therapies in Parkinson’s disease and related conditions.
https://perspectivesinmedicine.cshlp.org/content/16/1/a041891.full
In a paradigm-shifting thesis from Cold Spring Harbor Perspectives in Medicine, researchers (Schon, Matheoud, & Przedborski) dismantle the outdated view of Parkinson’s Disease (PD) as merely a “dying dopamine neuron” disorder. Instead, they reframe PD—and by extension, significant aspects of brain aging—as a systemic collapse of mitochondrial quality control that triggers a lethal immune response.
The “Big Idea” here is not just that mitochondria stop making energy (the classical ATP deficit model). It is that dysfunctional mitochondria, when not cleared by mitophagy (the cellular recycling crew), become toxic “antigen factories.” The authors highlight the PINK1-Parkin pathway, a mechanism that tags damaged mitochondria for destruction. When this pathway fails—due to aging or genetic mutations—damaged mitochondria release ancient bacterial-like DNA and proteins into the cytosol. This triggers the cGAS-STING pathway and other innate immune alarms, fooling the body into thinking it is under bacterial attack. The result is chronic, sterile neuroinflammation that cooks neurons alive.
For the longevity enthusiast, this paper is a “smoking gun” linking mitochondrial health directly to immune aging (inflammaging). It suggests that the path to preserving brain function isn’t just “boosting energy” with simple fuels, but aggressively enhancing the clearance of metabolic waste. The implications extend beyond PD: if you can keep your mitochondrial garbage disposal (mitophagy) running, you may delay the onset of neurodegeneration indefinitely.
Context:
Impact Evaluation: The impact score of this journal is ~7.8 to 10.1 (JIF), evaluated against a typical high-end range of 0–60+, therefore this is a High impact journal. While not a generalist giant like Nature, it is a premier “Elite” venue for deep-dive mechanistic reviews that define the consensus in molecular medicine.
The authors dissect the failure of the PINK1-Parkin Axis as the central driver of PD. Here is the biohacker breakdown:
Organ-Specific Priority: Substantia Nigra (Brain) and Gut-Brain Axis (early mitochondrial failure often starts in the intestine).
The paper moves the needle by cementing the link between Mitochondria and Immunity. It shifts the focus from “energy crisis” to “immune trigger.” It implies that anti-inflammatory drugs are band-aids, while mitophagy inducersare the actual cure. It also lends massive weight to the “intestine-first” hypothesis, where gut infection/stress triggers mitochondrial failure that propagates to the brain.
ALS is much the same. It starts with a failure of mitophagy and then everything else goes wrong.
I’m wondering if the peptide SS-31 might be helpful in preventing or mitigating PD:
What is the scientific and clinical evidence on whether or not the peptide SS-31 might be helpful in the mitochondria-related issues in Parkinson’s disease, as laid out in this paper?
Context: Evaluating efficacy for Parkinson’s Disease (PD) through the lens of the PINK1-Parkin/cGAS-STING axis.
Narrative: The peptide SS-31 (Elamipretide) is currently the closest pharmacological match to the “mitochondrial quality control” crisis described in your source paper. While most mitochondrial drugs try to “force” energy production (like whipping a tired horse), SS-31 works structurally. It selectively binds to cardiolipin—the unique phospholipid “glue” of the inner mitochondrial membrane. By stabilizing cardiolipin, it prevents the membrane fragmentation that allows mtDNA to leak into the cytosol.
The Big Idea: Your source paper identifies mtDNA leakage as the trigger for the cGAS-STING immune alarm in Parkinson’s. Recent data (2024/2025) confirms that SS-31 directly inhibits this specific pathway. By sealing the mitochondrial membrane, it stops the “antigen factory” problem at the source, preventing the neuroinflammation that kills dopaminergic neurons.
Clinical Reality: In September 2025, the FDA approved Elamipretide (brand name Forzinity) for Barth Syndrome, a rare genetic mitochondrial disease. For Parkinson’s, however, the data is split: “Standard” clinical trials (MMPOWER-3) failed in general mitochondrial myopathy, but post-hoc analysis revealed it worked significantly well in patients with nuclear DNA (nDNA) mutations—the exact type of genetic defect (like PINK1/Parkin) implicated in your paper.
Related Reading: Hazel Szeto, SS-31 and the World's First FDA-Approved Mitochondria-targeted Drug (Longevity Summit, 2025)
It may help, but you basically need to keep the mtDNA in a good shape.
@John_Hemming what is the best way we know of to accomplish this?
@RapAdmin after your post in the ss-31 thread, I did the same search and was excited to see that there is hope it might help. I wonder what the dosing protocol might look like? I’m currently taking 5mg per day.
A new study from UCLA Health has found that long-term residential exposure to the pesticide chlorpyrifos is associated with more than a 2.5-fold increased risk of developing Parkinson’s disease.
https://medicalxpress.com/news/2026-01-widely-pesticide-linked-parkinson.html
This article is interesting and we discussed it before: Parkinson's disease - #948 by adssx
The most interesting point is unfortunately not mentioned in the SciTechDaily article you shared:
Interestingly, S. mutans-induced decrease in brain weight in the antibiotic-treated mice was reversed by rapamycin treatment (Supplementary Fig. 3h).
Importantly, rapamycin treatment did not reduce the elevated levels of imidazole propionate induced by S. mutans in plasma and brain (Fig. 3e, f).
The increase in S6 and 4E-BP1 phosphorylation induced by S. mutans in the dopaminergic neurons of the substantia nigra was almost completely reversed by rapamycin treatment (Fig. 3g, Supplementary Fig. 3k), despite comparable elevations in imidazole propionate in the brain of S. mutans-colonized mice with or without rapamycin (Fig. 3f). In support of our hypothesis of mTORC1-dependent neurotoxicity, rapamycin treatment (mTORC1 inhibition) effectively prevented 4E-BP1 phosphorylation, dopaminergic neurodegeneration, astrogliosis, and microgliosis in the ventral midbrain, as well as the loss of dopaminergic processes in the substantia nigra reticularis and dopaminergic axon terminals in the striatum (Fig. 3h, i, and Supplementary Fig. 3k, l, m). Rapamycin also reversed motor dysfunction induced by S. mutans colonization in antibiotic-treated mice (Fig. 3j).
At the time I contacted the authors because they focused on pirfenidone in their conclusion and did not mention rapamycin: Parkinson's disease - #949 by adssx
They later answered:
Alternatively, if we were to describe the result itself, we could have written: “Imidazole propionate-induced neurotoxicity is inhibited by either rapamycin or the p38γ inhibitor pirfenidone (Supplementary Fig. 3c), suggesting that these agents may represent potential therapeutic options.”
And later:
Thank you. During the several rounds of revision, the emphasis of this manuscript has shifted, and I agree that this sentence is more closely aligned with our initial version. As I noted earlier, it would indeed have been preferable to include both rapamycin and pirfenidone in the sentence. I greatly appreciate your thoughtful feedback.
I’m waiting for the day Antoine hops on the rapamycin bandwagon 
! C’mon to the dark side 
… I’m kidding of course, but the way I look at it is even if rapa does nothing for any NDD, as long as it’s not actually a negative, then it’s worth a gamble for any other possible health benefits. Upside potential with very low downside risk (in my opinion). YMMV.
I did jump on the rapa bandwagon a few months ago and so far so good 
I had no idea! Well, congratulations, and I’m happy you are doing well! I had to pause my rapa due to surgery, will resume in April. I did notice that the effects of rapa change after being on it for months. Initially I used to get pimples for example, then these went away after about 6 months, even when I escalated the dose to 10mg once a week for 10 weeks (when I was misdiagnosed with frozen shoulder - it worked for Matt Kaeberlein, so I did that). Bottom line, don’t be surprised if the effects change with longer term use.
