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Related Experiment Video

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APLP1 Interacts with SARM1 and Regulates Axonal Maintenance and Post-Injury Degeneration.

Minjae Kang1,2, Hwigyeong Kim1,2, Yewon Jeon1

  • 1Peripheral Neuropathy Research Center (PNRC), Department of Molecular Neuroscience, College of Medicine, Dong-A University, 32 Daesingongwon-Ro, Seo-Gu, Busan, 49201, Republic of Korea.

Molecular Neurobiology
|December 1, 2025
PubMed
Summary

Amyloid beta precursor-like protein 1 (APLP1) binds to SARM1, a key enzyme in nerve degeneration. This interaction is crucial for maintaining peripheral nerve axons and preventing degeneration after injury.

Keywords:
APLP1Axon degenerationEmbryonic dorsal root gangliaGrowth coneSARM1

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Amyloid beta precursor-like protein 1 (APLP1) is linked to neurodegenerative diseases.
  • The function of APLP1 in the peripheral nervous system (PNS) is not well understood.
  • Sterile alpha and TIR motif-containing 1 (SARM1) is a critical NAD+ hydrolase regulating axonal degeneration in the PNS.

Purpose of the Study:

  • To investigate the role of APLP1 in the peripheral nervous system.
  • To identify regulators of SARM1-dependent axonal degeneration.
  • To elucidate the interaction between APLP1 and SARM1.

Main Methods:

  • Yeast two-hybrid screening was used to identify SARM1-binding proteins.
  • APLP1 was identified as a SARM1-binding protein.
  • APLP1 expression levels were analyzed after axonal injury in cultured neurons and mouse sciatic nerves.
  • APLP1 knockdown was performed to assess its effect on neuronal NAD+ levels and axonal degeneration.

Main Results:

  • APLP1 binds to the auto-inhibitory domain of SARM1.
  • APLP1 levels increase in proximal axons after injury.
  • APLP1 knockdown reduces neuronal NAD+ levels and causes spontaneous SARM1-dependent axonal degeneration.
  • APLP1 knockdown accelerates injury-induced axonal degeneration.

Conclusions:

  • APLP1 interacts with SARM1 and plays a role in axonal maintenance.
  • APLP1 is a novel regulator of SARM1-dependent axonal degeneration in the peripheral nervous system.
  • Targeting the APLP1-SARM1 interaction may offer therapeutic strategies for peripheral nerve injury.