Involvement of cyclin dependent kinase5 activator p25 on tau phosphorylation in mouse brain.
P35 or its truncated fragment p25 is required for cyclin dependent kinase (Cdk)5 activation. It has been reported that p25 is accumulated in the brain of Alzheimer's disease (AD) patients and that p25/Cdk5 induces high phosphorylation of tau and apoptosis in cultured neurons (Nature 402 (1999) 615). Our investigation of AD brain did not show specific accumulation of p25. Exposure to Ca ionophore (A23187) at 10(-6) M induced p25 accumulation in rat primary hippocampal neurons, causing neuronal death without showing hyperphosphorylation of tau. Transgenic mice expressing p25 showed the accumulation of p25 but neither hyperphosphorylation of tau nor neuronal death was shown in these mice. The feature of these mice was the progression of cell growth in pituitary gland. These results suggest that overexpression of p25 lead to the activation of cell cycle but not to the direct phosphorylation of tau.
Takashima
A
A
Laboratory for Alzheimer's Disease, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, 351-0198, Saitama, Japan. kenneth@brain.riken.go.jp
Murayama
M
M
Yasutake
K
K
Takahashi
H
H
Yokoyama
M
M
Ishiguro
K
K
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000201:enzymology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010900:Pituitary Diseases / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D016875:tau Proteins / Q000378:metabolism*
D007476:Ionophores; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D016875:tau Proteins; D000001:Calcimycin; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases