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The Neuronal Cell Cycle and Its Distinctive Features

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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.

The Neuronal Cell Cycle and Its Distinctive Features

The neuronal cell cycle refers to the series of events that neurons undergo from their birth to their eventual degeneration. Unlike other cell types, mature neurons in the adult brain do not typically divide. The cell cycle includes the G1 phase, where the cell grows and prepares for DNA synthesis; the S phase, where DNA replication occurs; and the G2 phase, where the cell prepares for mitosis. However, neurons usually enter a resting state called G0 and do not proceed with cell division. In some cases, such as 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 due to incomplete DNA replication or other disruptions.
Detailed neuron with dendrites, axon and myelin sheath in shades of beige and brown on a blurred background suggesting neural tissue.

Neuronal Cell Cycle Control Mechanisms

The neuronal cell cycle is regulated by a balance between cyclins and cyclin-dependent kinases (Cdks). Cyclins activate Cdks, which then phosphorylate specific target proteins to advance the cell cycle. During the G1 phase, cyclin D partners with Cdk4/6 to phosphorylate the retinoblastoma (Rb) protein, releasing the transcription factor E2F1, which is crucial for initiating DNA synthesis. The transition from G1 to S phase is further controlled by cyclin E and Cdk2. Cyclin A collaborates with Cdk2 and later Cdk1 to support DNA replication and prepare for mitosis. The G2/M transition is managed by the Cdk1/cyclin B complex. 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. These checkpoints are vital for preserving genomic stability and preventing unregulated cell proliferation.

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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.

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