HDAC

links: Enzyme reference: https://old.reddit.com/r/Nootropics/comments/596gbi/i_wrote_an_article_on_hdac_inhibitors_geared/ 10-18-2021

Histone Deacetylase #

• Remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone, which allows DNA to wrap more tightly. Hyperacetylated chromatin (euchromatin) is transcriptionally active, and hypoacetylated chromatin is silent.
  • This is a posttranslational modification, altering the chromatin structure such that it increases accessibility for transcriptional regulatory proteins.
• Subtypes:
  • I: HDAC1-3, 8.
  • IIA: HDAC4, 5, 7, 9
  • IIB: HDAC6, HDAC10
  • III: The Sirtuins.
  • IV: HDAC11
• They interact with a ton of proteins. Not heaps but y’know too many to list.
• Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation
  • Basically I’m an idiot reading this, but I think inhibition of HDAC increases CREB activity - but maybe mainly in a positive way.
    • I don’t think it actually did tho when I looked at the chart; all CREB products were a lower SEN number or whatever it is
    • TSA = HDAC inhibitor.
    • SEM = subsets expectation maximum
  • CREB is required for the enhancement of memory and synaptic plasticity by HDAC inhibition
    • CREB activates CBP which is associated with HAT activity.
• Inhibit with Vorinostat, and to some degree Resveratrol, EGCG.
• Associated with Cancer, I believe.
  • 
• Sometimes, fear extinction is nigh impossible after very salient induction (i.e. bell->shock - even after hearing the bell and no shock, the fear memory is actually reinforced). HDAC inhibition prolongs the window of the ‘updating’ phase and makes the situation more emotionally neutral.
• Histone acetylation regulates intracellular pH