The Role of HDAC6 in Alzheimer's Disease

The expression of histone deacetylase 6 (HDAC6)-a versatile enzyme with a known role in epigenetics-increases significantly in the hippocampus and other relevant brain regions in both patients with Alzheimer's disease (AD) and animal models of AD. However, when and how HDAC6 expression increases during the course of AD progression remains unclear. Whether HDAC6 overexpression is an underlying cause of AD or a condition resulting from AD is controversial. Mounting evidence suggests that increased HDAC6 expression contributes to AD-associated neurodegeneration, although beneficial effects have also been identified. This review article addresses recent research on HDAC6 structure and function, and highlights the potential detrimental and protective roles of HDAC6 overexpression in AD. We hope to shed light on whether HDAC6 overexpression is associated with AD etiopathogenesis or whether it rescues AD-associated neurodegeneration compensatorily. Furthermore, we discuss new evidence showing that HDAC6 may be a therapeutic target for AD.