Leveraging targeted kinase degradation as a novel therapeutic strategy for Alzheimer's disease.

Abstract

Despite recent advances, Alzheimer's disease (AD) remains largely a mystery more than a century after its discovery. Protein kinases are among the new targets under investigation, which is not surprising given their crucial role in maintaining cellular homeostasis and in the development of various diseases. Several protein kinase inhibitors have shown remarkable therapeutic efficacy in the context of AD, although none of them have yet received approval by regulatory agencies. Alongside the use of classic inhibitors, a new therapeutic approach has emerged in recent years, shifting the focus from modulation to targeted degradation of the protein. The purpose of this review is to highlight and discuss novel series of proteolysis-targeting chimeras (PROTACs) directed against protein kinases relevant to the development of AD.