Autophagy review

Macroautophagy/autophagy is an evolutionarily conserved pathway responsible for clearing cytosolic aggregated proteins, damaged organelles or invading microorganisms. Dysfunctional autophagy leads to pathological accumulation of the cargo, which has been linked to a range of human diseases, including neurodegenerative diseases, infectious and autoimmune diseases and various forms of cancer. Cumulative work in animal models, application of genetic tools and pharmacologically active compounds, has suggested the potential therapeutic value of autophagy modulation in disease, as diverse as Huntington, Salmonella infection, or pancreatic cancer. Autophagy activation versus inhibition strategies are being explored, while the role of autophagy in pathophysiology is being studied in parallel. However, the progress of preclinical and clinical development of autophagy modulators has been greatly hampered by the paucity of selective pharmacological agents and biomarkers to dissect their precise impact on various forms of autophagy and cellular responses. Here, we summarize established and new strategies in autophagy-related drug discovery and indicate a path toward establishing a more efficient discovery of autophagy-selective pharmacological agents. With this knowledge at hand, modern concepts for therapeutic exploitation of autophagy might become more plausible.

Full Paper (Open Access)

Interesting in lots of ways see lithium impact on autophagy

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I thought I would chase up the references on Lithium to see what dosing might be recommended:

I haven’t got the time to analyse this at the moment, but I hope to find the time in the near future.

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I have looked at this now. It looks at concentrations from 1mMol to 10mMol. 1mMol is the top end of the dosage for mental health issues and I would think there is a chance of nephrotoxcity at 10mMol.

I have been aiming myself for a concentration of about 50mcMol/L. Hence I am not sure that trying to increase autophagy with Lithium is a viable tactic. Its nice to know that it might be helping at a low point but I think it is likely to be minor.

The papers do raise a question as to whether to avoid extra inositol, however. That’s an issue for me as the RNA I supplement comes with extra inositol for a reason that I have not searched for.

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Of course inositol is widely sold and recommended as a supplement. I remember taking it myself as a supplement many years ago. It really makes one wonder at the taking of
supplements that were recommended in the past that have been proven to be ineffective or down right harmful. Fortunately for me, mabe, is I have been taking lithium in the form of lithium orotate as a supplement since ~1985.

Inositol: SUPPORTS HEALTHY MEMBRANE FUNCTION*: Inositol is found in all cell membranes, with the highest concentrations in the brain and central nervous system, where it plays an important role in neurotransmitter signaling.*

I continue to cull my supplement cupboard of many of the non essentials. I am not down to the level of Michael Lustgarten, but then I don’t eat, or have the desire to eat, as healthy a diet as he does. So what does it all mean Alphie? What is the optimal dose of lithium supplementation for a healthy person?

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This was interesting in parts but too long really

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