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Improved Histone Deacetylase Inhibitors as Therapeutics for the Neurodegenerative Disease Friedreich's Ataxia: A New Synthetic Route

Friedreich’s ataxia (FRDA) is caused by transcriptional repression of the nuclear FXN gene encoding the essential mitochondrial protein frataxin. Based on the hypothesis that the acetylation state of the histone proteins is responsible for gene silencing in FRDA, previous work in our lab identified a first generation of HDAC inhibitors (pimelic o-aminobenzamides), which increase FXN mRNA in lymphocytes from FRDA patients. Importantly, these compounds also function in a FRDA mouse model to increase FXN mRNA levels in the brain and heart.

Improved Histone Deacetylase Inhibitors as Therapeutics for the Neurodegenerative Disease Friedreich's Ataxia: A New Synthetic Route

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