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The Extrinsic Apoptotic Pathway01:17

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Related Experiment Video

Updated: Mar 21, 2026

An Ex Vivo Laser-induced Spinal Cord Injury Model to Assess Mechanisms of Axonal Degeneration in Real-time
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Axon degeneration: context defines distinct pathways.

Matthew J Geden1, Mohanish Deshmukh1

  • 1Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Current Opinion in Neurobiology
|May 20, 2016
PubMed
Summary
This summary is machine-generated.

Axon degeneration, crucial for development and injury, involves distinct pathways. While Wallerian degeneration focuses on SARM1 and NAD+ signaling, axon pruning and apoptosis share mechanisms but differ in caspase activation, with pruning requiring caspase-6 and apoptosis needing Apaf-1.

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Area of Science:

  • Neuroscience
  • Cell Biology

Background:

  • Axon degeneration is vital for neural development, plasticity, and injury repair.
  • Mammalian models study three main types: Wallerian degeneration, axon apoptosis, and axon pruning.
  • Distinct molecular pathways govern each degeneration context.

Purpose of the Study:

  • To elucidate the specific molecular mechanisms underlying different forms of axon degeneration.
  • To compare and contrast the signaling and execution pathways involved in Wallerian degeneration, axon apoptosis, and axon pruning.

Main Methods:

  • Review and synthesis of recent advances in axon degeneration research.
  • Analysis of signaling molecules (SARM1, NMNATs, NAD+, MAPK, DLK, JNKs, GSK3α/β) and executioners (Puma, Bax, caspases).

Main Results:

  • Wallerian degeneration involves SARM1, NMNATs, NAD+ depletion, and MAPK signaling.
  • Axon apoptosis and pruning share signaling (DLK, JNKs, GSK3α/β) and execution (Puma, Bax, caspase-9, caspase-3) pathways.
  • Caspase activation differs: apoptosis requires Apaf-1 (not caspase-6), while pruning requires caspase-6 (not Apaf-1).

Conclusions:

  • Distinct molecular mechanisms differentiate the three main contexts of axon degeneration.
  • Understanding these differences is key to comprehending neural development, plasticity, and injury response.
  • Specific caspase activation pathways highlight unique features of apoptosis versus pruning.