scholarly journals Commitment of 1-Methyl-4-phenylpyrinidinium Ion-induced Neuronal Cell Death by Proteasome-mediated Degradation of p35 Cyclin-dependent Kinase 5 Activator

2009 ◽  
Vol 284 (38) ◽  
pp. 26029-26039 ◽  
Author(s):  
Ryo Endo ◽  
Taro Saito ◽  
Akiko Asada ◽  
Hiroyuki Kawahara ◽  
Toshio Ohshima ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5

scholarly journals Interplay between MEK-ERK signaling, cyclin D1, and cyclin-dependent kinase 5 regulates cell cycle reentry and apoptosis of neurons

2012 ◽  
Vol 23 (18) ◽  
pp. 3722-3730 ◽  
Author(s):  
Prashant Kumar Modi ◽  
Narayana Komaravelli ◽  
Neha Singh ◽  
Pushkar Sharma
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Amyloid Peptide ◽  
Erk Signaling ◽  
Cyclin Dependent Kinase ◽  
Cell Cycle Reentry ◽  
Cyclin Dependent Kinase 5

In response to neurotoxic signals, postmitotic neurons make attempts to reenter the cell cycle, which results in their death. Although several cell cycle proteins have been implicated in cell cycle–related neuronal apoptosis (CRNA), the molecular mechanisms that underlie this important event are poorly understood. Here, we demonstrate that neurotoxic agents such as β-amyloid peptide cause aberrant activation of mitogen-activated kinase kinase (MEK)–extracellular signal-regulated kinase (ERK) signaling, which promotes the entry of neurons into the cell cycle, resulting in their apoptosis. The MEK-ERK pathway regulates CRNA by elevating the levels of cyclin D1. The increase in cyclin D1 attenuates the activation of cyclin-dependent kinase 5 (cdk5) by its neuronal activator p35. The inhibition of p35-cdk5 activity results in enhanced MEK-ERK signaling, leading to CRNA. These studies highlight how neurotoxic signals reprogram and alter the neuronal signaling machinery to promote their entry into the cell cycle, which eventually leads to neuronal cell death.

Roles of cyclin-dependent kinase 4 and p53 in neuronal cell death induced by doxorubicin on cerebellar granule neurons in mouse

2004 ◽  
Vol 365 (3) ◽  
pp. 180-185 ◽  
Author(s):  
Yuko Otsuka ◽  
Tomoaki Tanaka ◽  
Daigaku Uchida ◽  
Yoshihiko Noguchi ◽  
Naokatsu Saeki ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cyclin Dependent Kinase ◽  
Cerebellar Granule
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