<scp>GT</scp>
            1b functions as a novel endogenous agonist of toll‐like receptor 2 inducing neuropathic pain

Lim, Hadyanto; Lee, Jae-Sung; You, Byunghyun; Oh, Jin-Seok; Mok, Hyuck Jun; Kim, Yoo Sung; Yoon, Bo Eun; Kim, Byung Gon; Back, Seung Keun; Park, Jong Sang; Kim, Kwang Pyo; Schnaar, Ronald L.; Lee, Sung Joong

doi:10.15252/embj.2019102214

Cited by 20 publications

(20 citation statements)

References 57 publications

(82 reference statements)

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“…It also has been reported that there is a higher amount of GT1b found on sensory neurons than motor neurons in tissue collected from human cadavers 58 . In addition, it has been shown that injuries to the peripheral nervous system results in increased expression of ganglioside GT1b 59 . It may be possible that C2C binds some motor neurons but a combination of reduced uptake and insufficient GT1b-positive motor neurons leads to a difference in C2C activity in different neuron subtypes.…”

Section: Discussionmentioning

confidence: 99%

Intracellular G-actin targeting of peripheral sensory neurons by the multifunctional engineered protein C2C confers relief from inflammatory pain

Allen

Zhou

Wilhelm

et al. 2020

Sci Rep

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The engineered multifunctional protein C2C was tested for control of sensory neuron activity by targeted G-actin modification. C2C consists of the heptameric oligomer, C2II-CI, and the monomeric ribosylase, C2I. C2C treatment of sensory neurons and SH-SY5Y cells in vitro remodeled actin and reduced calcium influx in a reversible manner. C2C prepared using fluorescently labeled C2I showed selective in vitro C2I delivery to primary sensory neurons but not motor neurons. Delivery was dependent on presence of both C2C subunits and blocked by receptor competition. Immunohistochemistry of mice treated subcutaneously with C2C showed colocalization of subunit C2I with CGRP-positive sensory neurons and fibers but not with ChAT-positive motor neurons and fibers. The significance of sensory neuron targeting was pursued subsequently by testing C2C activity in the formalin inflammatory mouse pain model. Subcutaneous C2C administration reduced pain-like behaviors by 90% relative to untreated controls 6 h post treatment and similarly to the opioid buprenorphene. C2C effects were dose dependent, equally potent in female and male animals and did not change gross motor function. One dose was effective in 2 h and lasted 1 week. Administration of C2I without C2II-CI did not reduce pain-like behavior indicating its intracellular delivery was required for behavioral effect.

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Section: Discussionmentioning

confidence: 99%

Intracellular G-actin targeting of peripheral sensory neurons by the multifunctional engineered protein C2C confers relief from inflammatory pain

Allen

Zhou

Wilhelm

et al. 2020

Sci Rep

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“… 184 More recently, it was found that after peripheral nerve injury, GT1b ganglioside is axonally transported from the cell body of sensory neurons into the spinal cord and mediates neuropathic pain development through the activation of TLR2. 126 …”

Section: Mechanisms Of Sensory Neuron–associated Macrophages Activation and Accumulation After Nerve Injurymentioning

confidence: 99%

Sensory neuron–associated macrophages as novel modulators of neuropathic pain

Silva

Guimarães

Cunha

2021

PR9

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The peripheral nervous system comprises an infinity of neural networks that act in the communication between the central nervous system and the most diverse tissues of the body. Along with the extension of the primary sensory neurons (axons and cell bodies), a population of resident macrophages has been described. These newly called sensory neuron–associated macrophages (sNAMs) seem to play an essential role in physiological and pathophysiological processes, including infection, autoimmunity, nerve degeneration/regeneration, and chronic neuropathic pain. After different types of peripheral nerve injury, there is an increase in the number and activation of sNAMs in the sciatic nerve and sensory ganglia. The activation of sNAMs and their participation in neuropathic pain development depends on the stimulation of pattern recognition receptors such as Toll-like receptors and Nod-like receptors, chemokines/cytokines, and microRNAs. On activation, sNAMs trigger the production of critical inflammatory mediators such as proinflammatory cytokines (eg, TNF and IL-1β) and reactive oxygen species that can act in the amplification of primary sensory neurons sensitization. On the other hand, there is evidence that sNAMs can produce antinociceptive mediators (eg, IL-10) that counteract neuropathic pain development. This review will present the cellular and molecular mechanisms behind the participation of sNAMs in peripheral nerve injury–induced neuropathic pain development. Understanding how sNAMs are activated and responding to nerve injury can help set novel targets for the control of neuropathic pain.

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“…To the best of our knowledge, this is the first study to demonstrate the separation of GT1a and GT1b by RPLC. GT1b, along with GM1, GD1a, and GD1b, is one of the four major GGs in the human brain [45] whose role in axonmyelin stability [46] and toll-like receptor-2 signaling [47] has been reported. GT1a is considerably less abundant than GT1b [48,49], as also shown in our analysis (Figures 5B), and its biological function generally has been explored indirectly using immunochemical analyses [50,51].…”

Section: Evaluation Of Ammonium Bicarbonate Concentration For Lc−ms Of Gd1 and Gt1 Isomersmentioning

confidence: 99%

Isomer separation and analysis of amphiphilic polysialogangliosides using reversed‐phase liquid chromatography‐mass spectrometry

Park

Shrestha

Cha

2021

J of Separation Science

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Gangliosides are amphiphilic, acidic glycosphingolipids possessing one or more sialic acid residues and several isobaric structural isomers with different abundances and bioactivities. Therefore, the distinction between these isomers is crucial for their proper profiling. Although liquid chromatography-mass spectrometry has been successfully employed for this purpose, the distinction process can still be improved, particularly regarding liquid chromatography. Recently, a reversed-phase liquid chromatography method that could separate disialoganglioside isomers was reported; however, the distinction of trisialoganglioside isomers using reversed-phase liquid chromatography has not been demonstrated. Here, we investigated the practicality of a reversed-phase liquid chromatography with an octadecylsilane column for separating polysialoganglioside isomers and successfully achieved the isomer separation of disialogangliosides and trisialogangliosides for the first time. We also confirmed several crucial factors in the mobile-phase composition, which affect the differential retention and mass spectral response of the isomers. First, an organic modifier, acetonitrile, exhibited superior selectivity against polysialogangliosides over methanol. Second, ammonium bicarbonate was the best ammonium salt additive among those tested, in terms of the separation efficiency and mass spectral response. Third, as the ammonium salt concentration increased, the negative electrospray ionization response was extensively suppressed, and the retention of gangliosides increased.

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GT 1b functions as a novel endogenous agonist of toll‐like receptor 2 inducing neuropathic pain

Cited by 20 publications

References 57 publications

Intracellular G-actin targeting of peripheral sensory neurons by the multifunctional engineered protein C2C confers relief from inflammatory pain

Intracellular G-actin targeting of peripheral sensory neurons by the multifunctional engineered protein C2C confers relief from inflammatory pain

Sensory neuron–associated macrophages as novel modulators of neuropathic pain

Isomer separation and analysis of amphiphilic polysialogangliosides using reversed‐phase liquid chromatography‐mass spectrometry

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