2. Academic Validation
  3. GT1b functions as a novel endogenous agonist of toll-like receptor 2 inducing neuropathic pain

GT1b functions as a novel endogenous agonist of toll-like receptor 2 inducing neuropathic pain

  • EMBO J. 2020 Mar 16;39(6):e102214. doi: 10.15252/embj.2019102214.
Hyoungsub Lim 1,  Jaesung Lee 1,  Byunghyun You 1,  Jae Hoon Oh 2,  Hyuck Jun Mok 3,  Yoo Sung Kim 4,  Bo-Eun Yoon 4,  Byung Gon Kim 5,  Seung Keun Back 6,  Jong-Sang Park 2,  Kwang Pyo Kim 3,  Ronald L Schnaar 7,  Sung Joong Lee 1
Affiliations

Affiliations

  • 1 Department of Neuroscience and Physiology, Dental Research Institute, BK21-Plus, School of Dentistry, Seoul National University, Seoul, Korea.
  • 2 Department of Chemistry, Seoul National University, Seoul, Korea.
  • 3 Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yongin, Korea.
  • 4 Department of Molecular Biology, Dankook University, Cheonan, Korea.
  • 5 Department of Brain Science and Neurology, Ajou University School of Medicine, Suwon, Korea.
  • 6 Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon, Korea.
  • 7 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
PMID: 32030804 DOI: 10.15252/embj.2019102214
Abstract

Spinal cord microglia contribute to nerve injury-induced neuropathic pain. We have previously demonstrated that Toll-like Receptor 2 (TLR2) signaling is critical for nerve injury-induced activation of spinal cord microglia, but the responsible endogenous TLR2 Agonist has not been identified. Here, we show that nerve injury-induced upregulation of Sialyltransferase St3gal2 in sensory neurons leads to an increase in expression of the sialylated glycosphingolipid, GT1b. GT1b ganglioside is axonally transported to the spinal cord dorsal horn and contributes to characteristics of neuropathic pain such as mechanical and thermal hypersensitivity. Spinal cord GT1b functions as an TLR2 Agonist and induces proinflammatory microglia activation and central sensitization. Pharmacological inhibition of GT1b synthesis attenuates nerve injury-induced spinal cord microglia activation and pain hypersensitivity. Thus, the St3gal2-GT1b-TLR2 axis may offer a novel therapeutic target for the treatment of neuropathic pain.

Keywords

St3gal2; ganglioside; microglia; neuropathic pain; toll-like receptor 2.

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