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The neuronal cell cycle is a critical process for neuron function and survival, involving phases like G1, S, and G2, but avoiding cell division in mature neurons. This cycle is tightly regulated by cyclins and Cdks, with disruptions leading to diseases such as Alzheimer's. Neurons may re-enter the cycle in response to injury, often resulting in cell death. However, some neurons can replicate DNA without apoptosis, contributing to neuronal diversity and development.
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During the G1 phase, the cell grows and prepares for DNA synthesis
The S phase is where DNA replication occurs
The G2 phase is where the cell prepares for mitosis
Cyclins activate Cdks, which then phosphorylate specific target proteins to advance the cell cycle
Cell cycle inhibitors from the Ink4 and Cip/Kip families prevent premature activation of cyclin/Cdk complexes, ensuring that cells only progress when conditions are appropriate
Checkpoints are vital for preserving genomic stability and preventing unregulated cell proliferation
In response to injury or disease, neurons may attempt to re-enter the cell cycle, a process known as "abortive cell cycle re-entry," which can lead to cell death
Pathological triggers can induce an aberrant re-entry into the cell cycle, often leading to neuronal death
Tetraploid neurons, which contain double the normal amount of DNA, have been identified in various neuronal populations and can persist in a tetraploid state
In neurodegenerative diseases like Alzheimer's, neurons that aberrantly re-enter the cell cycle are more susceptible to apoptosis, which exacerbates the disease
The G2/M checkpoint seems to be critical for the survival of neurons in neurodegenerative disorders
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Neuronal cell cycle phases
Includes G1 (growth/prep for DNA synthesis), S (DNA replication), G2 (prep for mitosis).
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Mature neuron division in adult brain
Mature neurons typically do not divide; enter G0 resting state instead.
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Abortive cell cycle re-entry
Neurons may re-enter cell cycle due to injury/disease, leading to potential cell death.
