Re-entry into the cell cycle: a mechanism for neurodegeneration in Alzheimer disease.
Several recent findings demonstrated increased expression of cell cycle-related proteins in the degenerating neurons found in Alzheimer disease. We hypothesize that this apparent attempt to re-enter the cell cycle is a neuronal response to external growth stimuli that leads to an abortive re-entry into the cell cycle. However, since neurons of adults apparently lack the capacity both to divide in vivo and in vitro, it is possible that they lack the components necessary to complete the cell division process. Nonetheless, the importance of these findings is that they provide an explanation for the increased phosphorylation of cytoskeletal proteins such as tau and neurofilaments that represent the most striking intracellular changes in the disease. Further, it is our contention that inappropriate reentry into the cell cycle and interrupted mitotic processes are significant factors not only in the cytoskeletal pathology but also in the neuronal degeneration that characterizes the pathology of Alzheimer disease.
McShea
A
A
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington, USA.
Wahl
A F
AF
Smith
M A
MA
D000328:Adult; D000544:Alzheimer Disease / Q000473:pathology*; D002453:Cell Cycle; D006801:Humans; D008959:Models, Neurological; D009410:Nerve Degeneration