response to axon injury

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an axon injury stimulus. [GOC:dgh, GOC:dph, GOC:jid, GOC:lm]

Response to axon injury is a complex and highly regulated process that involves a cascade of cellular and molecular events aimed at restoring axonal function or, if irreparable, promoting degeneration and removal of the damaged segment.

**1. Injury Detection and Signal Transduction:**
- Upon axonal injury, a variety of signals are released from the damaged site, including calcium ions, reactive oxygen species, and signaling molecules like cAMP.
- These signals activate a range of intracellular signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.

**2. Early Response:**
- **Distal Axon Degeneration (Wallerian Degeneration):** This is a rapid and regulated process of axonal fragmentation and removal distal to the injury site.
- **Axonal Transport Disruption:** Injury disrupts anterograde and retrograde axonal transport, leading to the accumulation of organelles and proteins at the injury site.
- **Sealing of the Axon:** The axonal membrane seals quickly after injury to prevent further leakage of intracellular contents.

**3. Axon Regeneration:**
- **Growth Cone Formation:** At the proximal end of the injury, the axon forms a growth cone, a specialized structure that acts as a sensory and exploratory organ.
- **Guidance Cues:** Growth cones follow guidance cues, such as cell adhesion molecules and neurotrophic factors, to navigate through the injured tissue and towards the target.
- **Myelin Sheath:** In the peripheral nervous system, the Schwann cells, which form the myelin sheath, can help guide axon regeneration by forming myelin tubes and providing growth-promoting factors.

**4. Degeneration and Removal of Damaged Axon:**
- **Microglia and Macrophages:** These immune cells are recruited to the injury site and phagocytose cellular debris, including the damaged axon, ensuring clearance of the injury site.
- **Astrocytes:** These glial cells proliferate in response to injury and form a glial scar, which can both support axon regeneration and limit its progress in some cases.

**5. Functional Recovery:**
- **Synapse Formation:** If regeneration is successful, the regenerating axon forms new synapses with target cells, restoring functional connectivity.
- **Plasticity:** The nervous system demonstrates remarkable plasticity, and changes in neuronal activity and connections can compensate for injury-related loss of function.

**Factors influencing response to axon injury:**
- **Type of injury:** Different types of injuries (crush, transection, stretch) can elicit different responses.
- **Location of injury:** Injuries to the central nervous system often result in less effective regeneration compared to the peripheral nervous system.
- **Age and health status:** Age, health, and pre-existing conditions can influence the regenerative potential.

**Key Molecules Involved in Response to Axon Injury:**
- **Neurotrophic factors:** Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF).
- **Cell adhesion molecules:** L1, N-CAM.
- **Cytokines:** TNF-α, IL-1β.
- **Signaling proteins:** MAPK, PI3K/AKT, NF-κB.
- **Transcription factors:** c-Jun, ATF3.'"

Proteins (16)

Compounds (781)