Cdk5, a therapeutic target for Alzheimer's disease?
Alzheimer's disease (AD) represents the leading cause for senile dementia affecting more than 4 million people worldwide. AD patients display a triad of pathological features including brain atrophy caused by neuronal loss, beta-amyloid plaque and neurofibrillary tangles. We previously show that Cyclin-dependent kinase 5 (Cdk5) is deregulated in AD brains and may contribute to the pathogenesis of AD. In AD brains, a calpain cleavage product of its physiological regulator p35, p25 is elevated. p25 causes prolonged activation of Cdk5 and alteration of its substrate specificity. The implications of p25/Cdk5 in neurotoxicity, beta-amyloid plaque and neurofibrillary tangle pathology will be discussed.
Tsai
Li-Huei
LH
Department of Pathology, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA. li-huei_tesai@hms.harvard.edu
Lee
Ming-Sum
MS
Cruz
Jonathan
J
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases