The Role of Glycogen Synthase Kinase 3β in Alzheimer’s Disease, with Implications in Drug Design

Pp: 57-69 (13)

* (Excluding Mailing and Handling)

Abstract

The main neuropathological hallmark of Alzheimer's disease (AD) is the accumulation of aberrant hyperphosphorylated microtubule-associated protein tau, forming the intracellular neurofibrillary tangles and the extracellular deposits of β-amilóide peptide (βA). Glycogen Synthase Kinase-3β (GSK-3β), a serine/threonine kinase, has emerged as one of the most attractive therapeutic targets for the treatment of AD. This enzyme has been linked to all the primary abnormalities associated with Alzheimer’s disease, including hyperphosphorylation of the microtubule-associated protein tau, which contributes to the formation of neurofibrillary tangles, and its interactions with others Alzheimer’s disease-associated proteins. Thus, the significant role of GSK-3β in essential events in the pathogenesis of AD makes this kinase an attractive therapeutic target for neurological disorders. This chapter explores the nature and the structure of this promising enzyme, focusing on the structure-based design of new GSK-3β inhibitors.

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