regulation of neuron apoptotic process

Definition

Target type: biologicalprocess

Any process that modulates the occurrence or rate of cell death by apoptotic process in neurons. [GOC:go_curators, GOC:mtg_apoptosis]

Regulation of neuron apoptotic process is a complex and tightly controlled biological process that ensures the survival of healthy neurons while eliminating damaged or unnecessary ones. This intricate dance of life and death is orchestrated by a network of signaling pathways, involving both extrinsic and intrinsic mechanisms.

**Extrinsic Pathway:**

* **Death receptor activation:** Neurons express death receptors, such as TNF receptor 1 (TNFR1) and Fas receptor, on their cell surface. Binding of their respective ligands, TNF-α and Fas ligand, triggers the formation of the death-inducing signaling complex (DISC).
* **Caspase cascade activation:** The DISC recruits and activates caspase-8, an initiator caspase. Caspase-8 then activates effector caspases, such as caspase-3 and caspase-7, leading to the execution phase of apoptosis.

**Intrinsic Pathway (Mitochondrial Pathway):**

* **Stress-induced mitochondrial dysfunction:** Various stresses, including DNA damage, oxidative stress, and growth factor deprivation, can induce mitochondrial dysfunction. This leads to the release of pro-apoptotic proteins, such as cytochrome c, from the intermembrane space into the cytosol.
* **Apoptosis-inducing factor (AIF) release:** AIF, another pro-apoptotic protein, is also released from the mitochondria.
* **Caspase activation:** Cytochrome c and AIF activate caspase-9, another initiator caspase, which in turn activates effector caspases.
* **Execution phase:** Effector caspases dismantle the cell by cleaving key cellular components, such as proteins involved in DNA repair, cytoskeletal integrity, and nuclear envelope structure.

**Regulation:**

* **Anti-apoptotic factors:** Various anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, inhibit the release of pro-apoptotic proteins from mitochondria.
* **Survival factors:** Growth factors, such as nerve growth factor (NGF), activate signaling pathways that promote neuronal survival and inhibit apoptosis.
* **Transcriptional regulation:** Transcription factors, such as p53 and NF-κB, can regulate the expression of genes involved in both pro- and anti-apoptotic pathways.
* **Post-translational modifications:** Phosphorylation and ubiquitination of proteins can modulate their activity and influence the balance between pro- and anti-apoptotic pathways.

The balance between pro- and anti-apoptotic signals determines the fate of neurons. Dysregulation of these pathways can contribute to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and stroke.'
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Proteins (9)

Compounds (270)