Protein Phosphorylation is a Key Mechanism in Alzheimer's Disease

Altered protein phosphorylation states of several proteins are closely associated with Alzheimer's disease (AD). Among these are the amyloid-β protein precursor (AβPP) and the tau protein. In fact, altered protein phosphorylation states already provide strong biomarkers for AD diagnosis, as is the case with hyperphosphorylated tau. It follows that modulating signaling cascades provides an attractive avenue for exploring novel therapeutic strategies. This review focuses on some of the major protein kinases and protein phosphatases relevant to AD. Of particular relevance, posttranslational modifications dynamically regulate protein activity, subcellular localization, and stability. Protein phosphorylation states can mediate complex formation as well as regulate protein function, and this is important for cellular physiology but can likewise contribute to the development of neuropathological conditions. Furthermore, applying a system approach provides a more comprehensive understanding of the signaling events associated with AD and highlights possible convergence points that may contribute to the different AD pathological hallmarks.