Histone Deacetylases (Hdacs) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Histone Deacetylases (Hdacs) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues on histone proteins["@grff2013"], playing crucial [@dietz2010] roles in epigenetic regulation of gene expression["@grff2013"][@dietz2010][@grff2013]. Beyond histone modification, HDACs target numerous non-histone proteins involved in neuronal function, [@xu2011] synaptic plasticity, and neurodegeneration["@dietz2010"]. [@johnson2022]
Classification
Class I HDACs (Zn²⁺-dependent)
HDAC1 (18q22): Primarily nuclear, expressed in most tissues
HDAC2 (6q21): Neuronally enriched, critical for synaptic plasticity[@xu2011]
HDAC3 (5q31): Expressed in brain, associated with transcriptional repression
HDAC8 (Xp11.23): Primarily in smooth muscle and heart
The study of Histone Deacetylases (Hdacs) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development. [@consolidation2009]
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions. [@sleiman2009]
Dietz KC, Casaccia P, HDAC inhibitors and neurodegeneration: at the edge between magic bullets and magic poisons (2010)
Xu K, Dai XL, Huang HC, et al, Targeting HDACs: a promising therapy for Alzheimer's Disease (2011)
Johnson AA, Sathigramsiri K, Sheppard HM, et al, The role of HDACs in the response of the brain to metabolic stress (2022)
Simões-Pires C, Zwick V, Nurisso A, et al, HDAC6 as a target for neurodegenerative diseases: what makes it different from classical HDACs? J Alzheimers Dis (2013)
Unknown, consolidation of memory. Nat Rev Neurosci. 2009;10(9):615-620 (2009)
Sleiman SF, Basso M, Mahishi L, et al, Putting the 'kinase' in 'neurodegeneration': is HDAC a reasonable target? Expert Opin Ther Targets (2009)
Langley B, Gensert JM, Therapeutic targeting of REST in Huntington's Disease (2014)
Jia H, Morris CD, Williams RM, et al, HDAC6 inhibitor accelerates pathology and improves memory in a tauopathy mouse model (2019)
Chuang DM, Leng Y, Marinova Z, et al, Multiple roles of HDAC inhibition in neurodegenerative conditions (2009)
Pathway Diagram
The following diagram shows the key molecular relationships involving Histone Deacetylases (HDACs) discovered through SciDEX knowledge graph analysis: