Involvement of calpain and p25 of CDK5 pathway in ginsenoside Rb1's attenuation of beta-amyloid peptide25-35-induced tau hyperphosphorylation in cortical neurons.
Increasing evidence have shown that beta-amyloid (Abeta) induced hyperphosphorylation of tau, which eventually resulted in the disruption of microtubule (MT) integrity. Cyclin-dependent kinase 5 (CDK5) and its activator p35 are required for neurite outgrowth. The cleavage of p35 to p25, mediated by calpain and calcium, caused CDK5 dislocation and subsequently p25/CDK5-induced tau hyperphosphorylation, which disrupted the cytoskeleton and resulted in neuronal death. In the present study we investigated the effects of ginsenoside Rb1 on fibrillar Abeta(25-35)-induced tau hyperphosphorylation in primary cultured cortical neurons and also the potential involvement of Ca(2+)-calpain-CDK5 signal pathway. The present study suggests that Ca(2+), calpain, and p25 in CDK5 pathway may play important roles in Abeta(25-35)-induced tau hyperphosphorylation.
Chen
Xiaochun
X
Department of Neurology, Fujian Institute of Geriatrics, the Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China. chenxiaochun998@gmail.com
Huang
Tianwen
T
Zhang
Jing
J
Song
Jinqiu
J
Chen
Limin
L
Zhu
Yuangui
Y
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002154:Calpain / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016875:tau Proteins / Q000187:drug effects* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C089495:neuronal Cdk5 activator (p25-p35); D016875:tau Proteins; C442759:ginsenoside Rb1; D002154:Calpain; D002118:Calcium