Activating PP2A as a Therapeutic Intervention Strategy in Alzheimer's Disease
The reversible phosphorylation of proteins is a major cellular mechanism to rapidly modulate the activity of signal transduction networks. One of the key players that catalyze the removal of phosphate moieties from target proteins is the serine/threonine phosphatase, PP2A. The consequences of unbalanced phospho-regulation are epitomized by the tau protein, with unbridled phosphorylation of tau now thought to be a key step in the development of the tauopathies and neurodegenerative conditions such as Alzheimer's disease. Restoring tau phosphorylation to normal, physiological levels could be a productive therapeutic strategy. This review covers the structural aspects of PP2A formation and regulation and then focuses on certain compounds that may be utilized to boost the activity of certain tau relevant, PP2A species. The use of such compounds and their derivatives in the future may eventually increase the armentarium of useful therapeutics to treat one of the underlying causes of Alzheimer's disease.