Abortive oncogeny and cell cycle-mediated events in Alzheimer disease

2000 ◽  
pp. 235-242 ◽  
Author(s):  
Arun K. Raina ◽  
Xiongwei Zhu ◽  
Mervyn Monteiro ◽  
Atsushi Takeda ◽  
Mark A. Smith
Keyword(s):  
2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Mark A. Smith ◽  
Gemma Casadesus ◽  
Sandy L. Richardson ◽  
George Perry ◽  
Robert B. Petersen ◽  
...  

2000 ◽  
Vol 59 (10) ◽  
pp. 880-888 ◽  
Author(s):  
Xiongwei Zhu ◽  
Catherine A. Rottkamp ◽  
Heather Boux ◽  
Atushi Takeda ◽  
George Perry ◽  
...  

Author(s):  
Vladan Bajić ◽  
Bo Su ◽  
Hyoung-Gon Lee ◽  
Wataru Kudo ◽  
Sandra Siedlak ◽  
...  

AbstractPost-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11p110) throughout the cell cycle, a 58-kDa protein (CDK11p58) that is specifically translated from an internal ribosome entry site and expressed only in the G2/M phase of the cell cycle, and a 46-kDa protein (CDK11p46) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-β25–35 resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD.


2004 ◽  
Vol 25 ◽  
pp. S40
Author(s):  
Xiongwei Zhu ◽  
Andrew McShea ◽  
Peggy L. Harris ◽  
Arun K. Raina ◽  
Rudy J. Castellani ◽  
...  

Author(s):  
David J. Bonda ◽  
Hyun-pil Lee ◽  
Wataru Kudo ◽  
Xiongwei Zhu ◽  
Mark A. Smith ◽  
...  

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-β plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.


2009 ◽  
Vol 119 (12) ◽  
pp. 3692-3702 ◽  
Author(s):  
Nicholas H. Varvel ◽  
Kiran Bhaskar ◽  
Maria Z. Kounnas ◽  
Steven L. Wagner ◽  
Yan Yang ◽  
...  

1997 ◽  
Vol 56 (5) ◽  
pp. 592
Author(s):  
Andrew McShea ◽  
Peuev L. R ◽  
Harris Kevin Webster ◽  
Alan Wahl ◽  
Mark A. Smith
Keyword(s):  

2000 ◽  
Vol 21 ◽  
pp. 267 ◽  
Author(s):  
Xiongwei Zhu ◽  
Arun K. Raina ◽  
Catherine A. Rottkamp ◽  
Heather Boux ◽  
Sandra L. Siedlak ◽  
...  

2006 ◽  
Vol 2 ◽  
pp. S443-S443
Author(s):  
Mark A. Smith ◽  
Laura A. Previll ◽  
Meredith E. Crosby ◽  
Xiongwei Zhu ◽  
Robert Bowser ◽  
...  

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