Tau as a Therapeutic Target for Alzheimers Disease

A.      Boutajangout; E.      M. Sigurdsson; P.      K. Krishnamurthy

Abstract

Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of Alzheimers disease (AD) and are primarily composed of aggregates of hyperphosphorylated forms of the microtubule associated protein tau. It is likely that an imbalance of kinase and phosphatase activities leads to the abnormal phosphorylation of tau and subsequent aggregation. The wide ranging therapeutic approaches that are being developed include to inhibit tau kinases, to enhance phosphatase activity, to promote microtubule stability, and to reduce tau aggregate formation and/or enhance their clearance with small molecule drugs or by immunotherapeutic means. Most of these promising approaches are still in preclinical development whilst some have progressed to Phase II clinical trials. By pursuing these lines of study, a viable therapy for AD and related tauopathies may be obtained.

Keywords: Tau, therapy, kinases, phosphatase, aggregation, immunotherapy, neurodegenerative disorder, SORL1, PHF, Alz 50, immunoblotting