The Rhyothemis princeps Brain Externalization Project

 Learned about PON1 and PD yesterday by attending web conference presentation by Beate Ritz: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922777/ Anthocyanins increase PON1 and are thought to protective against PD, but they also increase NO production - hmm .... ~ Vitamin D levels are decreased in PD: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267215/ "After the discovery that the VDR and 1α-hydroxylase, the enzyme that converts vitamin D to its active form, were highly expressed in the substantia nigra, it was hypothesized that inadequate levels of circulating vitamin D may lead to dysfunction or cell death within the substantia nigra ( 25 , 26 )." Active vit D (calcitriol) is mainly produced in the kidneys, as is klotho. a-syn is produced in the kidneys throughout lifespan.  ~ Chronic kidney disease prevalence is lower in PD patients: https://www.mdsabstracts.org/abstract/prevalence-of-chronic-kidney-disease-in-patients-with-idiopathic-parkinsons-disease-in-a-tertia

MCC950, an NLRP3 inflammasome inhibitor, was shown to reverse symptoms in two Parkinson's disease mouse models and was reported to have no toxicity issues. The only reason given in the following article for not pursuing clinical trials is that it is off-patent: https://www.genengnews.com/news/parkinsons-disease-drug-that-cools-brains-on-fire-could-enter-human-trials-in-2020/   Given its mechanism of action it could be broadly effective against neurodegenerative diseases and even spinal cord injury ( https://www.frontiersin.org/articles/10.3389/fmolb.2020.00037/full ).   Infections due to immunosuppression may be a problem, but there are reasons to think that MCC950 would be safer than immunosuppressive agents currently used to treat inflammatory conditions:   "Thus, specific targeting of NLRP3 will not result in the complete blockade of IL-1β during infection and antimicrobial responses may remain intact. MCC950 may therefore have less immunosuppressive effects when compa

Autophagy and Neurodegeneration │ Prof. David Rubinsztein   https://www.youtube.com/watch?v=BgIk9ehY09k 30:00 screening for mTOR independent autophagy inducing drugs 37:08 felodipine, a Ca channel blocker, induces autophagy and clears protein aggregates 46:00 vicious cycle of protein aggregates impairing autophagy -> more protein aggregates ~  Glycine and tryptophan lower uric acid levels in patients with mild hyperuricemia: https://pubmed.ncbi.nlm.nih.gov/30845731/ Glycine is inversely correlated  with serum uric acid in healthy people and in lifestyle-related diseases: https://www.nature.com/articles/s41598-017-17710-6 The Nature article also notes men are more likely to have hyperuricemia and that estrogen promotes uric acid excretion. The SURE-PD trial of inosine to increase serum and CSF urate was halted due to lack of efficacy, BUT inosine was found to be effective in increasing urate and decreased rate of progression in women: https://pubmed.ncbi.nlm.nih.gov/31484712/ Gelatin

  Genetic Mutations in Parkinson's Disease | 2019 Udall Center Research Symposium, presented by Dr Valina Dawson Some very nice slides. 18:18 - 3:00 - 3:26   19:25 It is disappointing to see therapies targeting NLRP3 inflammasome inhibition are not more advanced, considering the success of MCC950 in mouse models and how broadly effective it could be for neurodegenerative diseases as well as spinal cord injury . Index   3:00 autosomal recessive PD (ARPD) genes & their functions   3:26 interaction of ARPD genes - 'linked in circuits' - leading to inactivation of Parkin & activation of PARP1 resulting in death of neurons   4:56 autosomal dominant - point mutations in alpha synuclein which facilitate its misfolding; a- syn can be duplicated or triplicated     6:00 VPS 35 - vacuolar sorting protein     6:54 LRRK2 - sporadic PD - spontaneous mutations occur at high frequency - 1-7% of PD patients of European origin and 20-40% of PD in Ashkenazi Jews and North A

Getting even worse at keeping up with / track of things. So this week I read more about amino acids.   Lysine + arginie was found to help with anxiety and depression in a brief (7 day) trial. https://pubmed.ncbi.nlm.nih.gov/17510493 Lysine, threonine and histidine were found to inhibit mTOR in bone marrow derived mast cells and also ameliorate autism symptoms in a mouse model. https://pubmed.ncbi.nlm.nih.gov/27640900 A bit weird that histidine ameliorated autism symptoms since histidine converts to histamine and there is indirect evidence of mast cell involvement in autism. However, histidine supplements are used by naturopaths to treat allergy since there is apparently a paradoxical effect -  I need to find a peer-reviewed reference source for this. A metabolomics study found threonine to be elevated in a mouse model of PD; glycine was lowered and urea was higher. Mannose was elevated. https://pubmed.ncbi.nlm.nih.gov/32937957 Came across an anecdote on amazon reviews of threonine reli