PDF figure 1 CELL CYCLE MECHANISMS AND NEURONAL CELL DEATH Biology Diagrams Cell cycle re-entry in neurons and tetraploidy. There are cases in which neuronal injury results in G1/S transition and DNA synthesis. Examples of this situation are cerebellar granule neurons subjected to excitotoxic stimuli 61 and cortical and hippocampal neurons subjected to hypoxia/reperfusion. 62 Although terminally differentiated neurons that replicate their DNA are typically fated to The expression of cell-cycle markers in the brain of AD patients was first described at the beginning of the 1990s (Baumann et al. 1993; Vincent et al. 1996).Although this discovery was surprising, since neurons do not proliferate but remain in a quiescent state (also known as the G0 phase of the cell cycle), it did appear to implicate the cell cycle in the process of neuronal loss. The role of the cell cycle in such disorders is supported by data on the brain of patients who showed an increase in cell-cycle protein expression. Indeed, studies performed in neuronal cell preparations indicate that oxidative stress could be the main mechanism responsible for cell cycle re-entry.
The candidate inducers of cell cycle re-entry in neurons The molecular mechanisms behind the cell death associated with cell cycle re-entry seem to be closely involved with oxidative stress. As both phenomena are manifest early in the pathogenesis of AD, and as mature cases of AD exhibit markers of both (Refs 18 , 60 ), it seems clear that Thus, cell cycle re-entry into adult neurons constituted an early signature of neuromuscular degeneration and CNS injury. Table 2. A consolidated list of various cell cycle markers that actively participate in post-mitotic neurons and related disorders as listed (shaded in gray); (โ) indicates no reported action of that particular cell cycle
Neuronal cell cycle: the neuron itself and its circumstances Biology Diagrams
Neurons are usually regarded as postmitotic cells that undergo apoptosis in response to cell cycle reactivation. Nevertheless, recent evidence indicates the existence of a defined developmental program that induces DNA replication in specific populations of neurons, which remain in a tetraploid state for the rest of their adult life. By contrast, work over the last two and a half decades has discovered a link between cell-cycle reentry in neurons and several neurodegenerative conditions. In this context, neuronal cell cycle re-entry is widely considered to be aberrant and deleterious to neuronal health. In this review, we highlight historical and emerging reports of Recent evidence suggests that cell cycle genes become re-activated in some post-mitotic neurons in the aged brain. In this study, the authors develop a bioinformatic approach to robustly characterize the prevalence, nature, and fate of these cell cycle re-entry neurons, within the healthy aging and diseased human brain.
These 'cycling' neurons seem to be consigned to one of two fates depending on their stage of maturation: in young differentiating neurons, re-entry into a cell cycle leads to death within hours
