The Rhyothemis princeps Brain Externalization Project

Mutations in the gene that codes for LRRK2, a kinase, are a risk factor for Parkinson's disease . Increase in the kinase activity of LRRK2 caused by these mutations leads to increased apoptosis and neuronal loss in PD.   Vitamin B12 inhibits LRRK2 kinase activity: https://pubmed.ncbi.nlm.nih.gov/21198553/   "Herein we identify 5'-deoxyadenosylcobalamin (AdoCbl), a physiological form of the essential micronutrient vitamin B 12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity. Multiple assays show that AdoCbl directly binds LRRK2, leading to the alterations of protein conformation and ATP binding in LRRK2. ... Our study uncovers vitamin B 12 as a novel class of LRRK2 kinase modulator with a distinct mechanism, which can be harnessed to develop new LRRK2-based PD therapeutics in the future. "   High B12 status has been found to be associated with increased  risk of lung cancer: "Circulating concentrations of vitamin B12, based on pre-diagno...

  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 ...