Aberrant phosphorylation in the pathogenesis of Alzheimer's disease.
The modification of proteins by reversible phosphorylation is a key mechanism in the regulation of various physiological functions. Abnormal protein kinase or phosphatase activity can cause disease by altering the phosphorylation of critical proteins in normal cellular and disease processes. Alzheimer's disease (AD), typically occurring in the elderly, is an irreversible, progressive brain disorder characterized by memory loss and cognitive decline. Accumulating evidence suggests that protein kinase and phosphatase activity are altered in the brain tissue of AD patients. Tau is a highly recognized phosphoprotein that undergoes hyperphosphorylation to form neurofibrillary tangles, a neuropathlogical hallmark with amyloid plaques in AD brains. This study is a brief overview of the altered protein phosphorylation pathways found in AD. Understanding the molecular mechanisms by which the activities of protein kinases and phosphatases are altered as well as the phosphorylation events in AD can potentially reveal novel insights into the role aberrant phosphorylation plays in the pathogenesis of AD, providing support for protein phosphorylation as a potential treatment strategy for AD.
Chung
Sul-Hee
SH
Graduate Program in Neuroscience, Institute for Brain Science and Technology, Inje University, Busan 614-735, Korea. sulchung@inje.ac.kr
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D053763:Presenilins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism
D053763:Presenilins; D011494:Protein Kinases; D053829:Amyloid Precursor Protein Secretases