Freidriech ataxia - biochemical mechanisms

Yesterday I watched two excellent presentations on Freidreich ataxia (still trying to use the proper nomenclature convention) from back in 2011:


Notes:
5:44 frataxin is essential for muticellular eukaryotes (but not single celled organisms) frataxin is needed for the production of iron-sulfur clusters (aconitase is an important TCA enzyme that includes an iron-sulfur cluster that is particularly vulnerable to oxidation)
13:07 Indeed! & also part of the urea cycle
18:35 Reduction in frataxin leads to iron accumulation in the mitochondrion 
38:26 summary of therapeutic approaches in relation to hypothetical vicious cycle in FA
EPO - erythropoietin increases expression of genes related to iron utilization (lactoferrin and Wim Hof method breathing increase EPO)
HDAC inhibitors increase expression of frataxin (butyrate / tributyrin are HDACi) pioglitozone increases mitochondrial biogenesis (PQQ & urolithin A do the same)

I think neuroinflammation should be included as part of the vicious cycle / therapeutic targets.

Omaveloxolone, an Nrf2 activator, has been shown to improve neurological function of FA patients in a clinical trial.


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