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Regulation of autophagy by AMP-activated protein kinase/sirtuin 1 pathway reduces spinal cord neurons damage

Peng Yan1, Liangjie Bai1, Wei Lu1

  • 1Department of Orthopaedic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.

Iranian Journal of Basic Medical Sciences
|November 1, 2017
PubMed
Abstract

Insights

Activating the AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) pathway helps repair spinal cord injury (SCI) by improving autophagy and reducing neuron damage. This pathway shows potential for treating SCI.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • The AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway regulates autophagy in various biological models.
  • Autophagy plays a critical role in cellular homeostasis and response to injury.

Purpose of the Study:

  • To investigate the role of the AMPK/SIRT1 pathway in regulating autophagy following spinal cord injury (SCI).
  • To evaluate the therapeutic potential of modulating this pathway for SCI treatment.

Main Methods:

  • Established rat spinal cord injury (SCI) and primary neuron mechanical injury (MI) models in vivo and in vitro.
  • Assessed apoptosis using TUNEL and Hoechst staining.
  • Quantified autophagy-related proteins (LC3II/LC3I, p62) and AMPK/SIRT1 activation via Western blot and immunohistochemistry.
  • Utilized resveratrol to activate the AMPK/SIRT1 pathway.

Main Results:

  • Spinal cord trauma induced significant apoptosis and impaired autophagy, evidenced by altered LC3II/LC3I and p62 levels.
  • p-AMPK and SIRT1 levels increased post-trauma, indicating pathway activation.
  • Resveratrol treatment alleviated neuronal damage and restored autophagic flux by downregulating p62.
  • AMPK/SIRT1 pathway activation demonstrated a protective effect against SCI-induced neuronal damage.

Conclusions:

  • Modulation of the AMPK/SIRT1 pathway effectively regulates autophagy and mitigates neuronal damage after SCI.
  • The AMPK/SIRT1 pathway represents a promising therapeutic target for interventions in spinal cord injury.
Keywords:
AMPK/SIRT1 pathwayAutophagy fluxResveratrolSpinal cord injuryp62

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