Cell Cycle: Bringing Life or Death?
Most cells in the body undergo a constant process of formation, maturation, and division—this is called the cell cycle and it’s an essential part of normal life and growth. Neurons are different, however. Once formed, they generally do not divide. Forcing a mature neuron to reenter the cell cycle and undergo cell division will cause it to die (Herrup et al., 2004).
Based on findings from recent studies showing that the vulnerable neurons in AD brains contain proteins related to entry into the cell cycle, some researchers now hypothesize that the death of neurons in AD may be related to abnormal initiation of the cell cycle in these cells. Researchers at Case Western Reserve University, in Cleveland, Ohio, found that the cell-cycle process was initiated in three different transgenic mouse models of AD in a pattern similar to that seen in human AD (Yang et al., 2006). Unlike human AD, though, the mouse neurons did not die. These results suggested to the research team that although cell-cycle events may be necessary to cause the death of neurons, they are not sufficient, and that a second, triggering, event may be needed to cause cell death. Another key finding of the study was that the cell-cycle process in these mice began before beta-amyloid plaques or NFTs began to accumulate, once more suggesting that earlier forms of beta-amyloid may be the molecular trigger. Significantly, this cell-cycle process in these mouse models closely mimics that in humans with AD, thereby supporting the utility of these models in AD research, even in the absence of cell death or formation of NFTs.
Scientists at the Brigham and Women’s Hospital and Harvard Medical School have been pursuing a similar line of investigation by using Drosophila flies to study the impact of activating the cell-cycle process in neurodegenerative diseases, like AD, that feature abnormal deposits of tau protein (Khurana et al., 2006). These researchers found that activating the cell-cycle process caused tau-induced neurodegeneration, and interfering with the process substantially reduced neurodegeneration.
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