Arc: a therapeutic hub for Alzheimer's disease.

Alzheimers disease (AD) is poised to reach epidemic levels as the world population ages. There is currently no treatment that halts this debilitating disease. Our recent finding that the memory gene Arc regulates the expression of many genes associated with the pathophysiology of AD sets the stage for a new therapeutic approach that is not structurally based on the amyloid hypothesis that has driven most research to date. Neuronal activity-dependent Arc expression is controlled by a chromatin-modification complex containing two enzymes: Tip60 and PHF8. Here, we show that small molecules targeting these proteins inhibit Arc expression. This finding sets the stage for a novel therapeutic approach to combat Alzheimers disease. Targeting Arc opens a new frontier of "multi-target" therapy designed to intervene in several aspects of the disease simultaneously. Because of Arcs role in controlling the expression of multiple genes and pathways implicated in AD, it could serve as a therapeutic hub.