neuron apoptotic process

Definition

Target type: biologicalprocess

Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [CL:0000540, GOC:mtg_apoptosis]

Neuron apoptosis is a complex and tightly regulated process that involves a series of biochemical events leading to the programmed death of a neuron. This process plays a crucial role in neuronal development, maintaining neuronal homeostasis, and eliminating damaged or unnecessary neurons.

**1. Initiation:**
- **Extrinsic pathway:** Initiated by external stimuli like neurotrophin withdrawal, glutamate excitotoxicity, or exposure to toxins. These signals activate death receptors (e.g., TNF receptor) on the neuron's surface, triggering a cascade of intracellular signaling.
- **Intrinsic pathway:** Triggered by internal stress signals such as DNA damage, oxidative stress, or mitochondrial dysfunction. This pathway involves the release of cytochrome c from mitochondria into the cytoplasm.

**2. Execution:**
- **Caspase activation:** Both extrinsic and intrinsic pathways converge on the activation of a family of cysteine proteases called caspases. Caspases are initially present as inactive precursors (procaspases).
- **Caspase cascade:** Once activated, caspases form a proteolytic cascade, cleaving and activating downstream caspases.
- **Cleavage of cellular substrates:** Activated caspases cleave a variety of cellular substrates, leading to the disassembly of the cell.

**3. Cellular dismantling:**
- **DNA fragmentation:** Caspases cleave DNA repair enzymes and activate DNA endonucleases, resulting in the fragmentation of nuclear DNA into characteristic ladder-like patterns.
- **Cytoskeleton breakdown:** Caspases cleave proteins involved in maintaining cell structure and shape, leading to the collapse of the cytoskeleton.
- **Membrane blebbing:** The plasma membrane undergoes blebbing, forming small protrusions that detach from the cell.
- **Apoptotic bodies:** The apoptotic cell fragments into small, membrane-bound vesicles called apoptotic bodies. These bodies contain cellular debris and are readily phagocytosed by neighboring cells or macrophages.

**4. Phagocytosis and removal:**
- Apoptotic bodies are rapidly engulfed by surrounding cells or macrophages, preventing the release of cellular contents into the extracellular environment and minimizing inflammation.

**5. Molecular regulators:**
- Various proteins regulate neuron apoptosis, including:
- **Bcl-2 family:** This family of proteins plays a central role in regulating mitochondrial membrane permeability and cytochrome c release.
- **IAPs (inhibitor of apoptosis proteins):** These proteins inhibit caspase activity.
- **Death receptors:** These transmembrane proteins bind to external death signals.

**6. Significance:**
- **Developmental pruning:** Neuron apoptosis is essential for eliminating unnecessary or damaged neurons during development, shaping the neuronal circuitry.
- **Homeostatic maintenance:** Apoptosis removes aging, damaged, or dysfunctional neurons, maintaining neuronal homeostasis and ensuring normal brain function.
- **Neurodegenerative diseases:** Dysregulation of apoptotic pathways can contribute to the development of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.'
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Compounds (3,304)