Cyclin' toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease.
Recent evidence has associated the aberrant, proximal re-expression of various cell cycle control elements with neuronal vulnerability in Alzheimer disease, a chronic neurodegeneration. Such ectopic localization of various cyclins, cyclin-dependent kinases, and cyclin inhibitors in neurons can be seen as an attempt to re-enter the cell cycle. Given that primary neurons are terminally differentiated, any attempted re-entry into the cell division cycle in this postmitotic environment will be dysregulated. Since successful dysregulation of the cell cycle is also the hallmark of a neoplasm, early cell-cycle pathophysiology in Alzheimer disease may recruit oncogenic signal transduction mechanisms and, hence, can be viewed as an abortive neoplastic transformation.
Raina
A K
AK
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Zhu
X
X
Rottkamp
C A
CA
Monteiro
M
M
Takeda
A
A
Smith
M A
MA
D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D016213:Cyclins / Q000502:physiology*; D006801:Humans; D009857:Oncogenes / Q000502:physiology*
D016213:Cyclins