HDAC Inhibitors as Novel Therapeutics in Aging and Alzheimer’s Disease

Population aging is leading to an increase in age-related cognitive disorders, the most prevalent being Alzheimer’s disease. Mechanisms underlying cognition occur through changes in the expression of neuronal activity-dependent genes and neuroplasticity. These changes in gene expressions are regulated by epigenetic post-translational modifications to the chromatin structure. It is now becoming evident that many age-related human cognitive diseases are a consequence of aberrant chromatin-mediated neuroplasticity. Understanding the molecular nature of epigenetic mechanisms in the nervous system has the potential to provide new future therapeutic avenues for cognitive disease. In this chapter, we outline the role of the histone deacetylase (HDAC) family of chromatin modifying enzymes in regards to neurobiology and cognition. We discuss the chemistry of HDAC inhibitors, their biological effects on learning and memory, and their potential relevance towards developing therapeutics to enhance neuroplasticity and memory. Finally, we open suggestions as to where the field of HDAC pharmacology in relation to cognition should be directed.