Glycogen synthase kinase3β: A key player of cognitive dysfunction in chronic kidney disease patients and a possible link between abnormal pTau and platelet APP processing and therapeutic role of erythropoietin

Abstract

Glycogen synthase kinase3β (GSK3β) is connected to several important organic processes like glycogen metabolism, apoptosis, protein synthesis, cell signaling, cell transport, gene transcription, proliferation, and intracellular communication. Accordingly, GSK3β has been implicated in a wide variety of diseases, and various pharmaceutical organizations depend on GSK3β as a therapeutic target for disease remedy. Erythropoietin (EPO) is used routinely to treat anemia in chronic kidney disease (CKD). However, increasing evidence from human and animal studies has shown that treatment with EPO can improve hemoglobin and cognitive function. The aims of the review paper clarify the potential significance of GSK3β in anemic CKD patients with cognitive dysfunction as a multipotent molecular mechanism of change of platelets induced by EPO. Previously, we investigated the therapeutic effect of EPO on abnormal platelet amyloid precursor protein processing and expression, and also analyzed the relationship between abnormal platelet GSK3β expressions, plasma β amyloid (Aβ), total Tau, phosphorylated tau 181 (ptau-181) levels in patients with cognitive dysfunction with complete neuropsychological test scores (Mini Mental scale examination (MMSE), Wechsler memory scale (WMS I) and Tower of London (TOL)). We then highlight evidence indicating that GSK3β influences platelet expression in patients with cognitive impairment with anemic CKD, and how this may support targeting more effective therapies particularly for cognitive dysfunction in patients with CKD. We conclude by suggesting how to further advance this clinical development field, such as the use of EPO treatment pharmacogenomics studies in patients with anemic CKD with cognitive dysfunction.