Activation of the PD-1 pathway for Pain therapy: Glycine, a non-essential amino acid and neurotransmitter, increases the expression of PD-L1, attenuates acutes and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability via up-regulation of its target gene, 1/December/2017, 12.36 am

Molecular therapy for muscle atrophy and wasting: Cilostazol, a phosphodiesterase inhibitor used in the treatment of Peripheral vascular disease, increases the expression of FGF19 and its receptor ß-Klotho, phosphorylates ERK1/2 and S6K1, decreases the expression of tumor suppressors  genes, promotes regeneration of muscle cells and hypertrophy of skeletal muscle, and reverses muscular atrophy and wasting via up regulation of its target gene, 1/December/2017, 12.03 am
November 30, 2017
Antiviral therapy for HIV virus:  A pharmaceutical mixture encompassing  Cidofovir and Ribavirin (CR) increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production via up regulation of its target gene, 1/December/2017, 5.22 pm
December 1, 2017
Show all

Introduction:What they say:

A recent study from Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, US shows that “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.” This study was published in the 22 May 2017 issue of Nature Neuroscience (one of the best journals in Neurobiology with an impact factor of 16.724+) by Prof Ji RR, Chen G and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Activation of the PD-1 pathway for Pain therapy: Glycine, a non-essential amino acid and neurotransmitter, increases the expression of PD-L1, attenuates acutes and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability via up-regulation of its target gene


What is known?

It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year. However, the work published recently, which is described below, may highlight the caveat in such an approach, as blocking PD-L1 may promote spontaneous pain and allodynia in cancer-bearing mice.

Prof. Ji has shown recently that: (1) Programmed cell death ligand-1 (PD-L1), produced by melanoma and normal neural tissues, inhibits acute and chronic pain; (2) injection of PD-L1 alleviates pain, and thereby functions as an analgesic agent; (3) Neutralization of PD-L1 or Block of PD1 promotes mechanical allodynia (hypersensitivity to pain); (4) PD1 null mice suffers from thermal and mechanical hypersensitivity; (5) PD-L1 promotes phosphorylation of SHP-1 and inhibits Sodium channels via PD-1 activation; and (6) PD-L1 inhibits nociceptive neuron excitability in dorsal root ganglion and thereby functions as a neuromodulator, suggesting that increasing the expression or the level of PD-L1/PD1 may alleviate pain and thermal and mechanical hypersensitivity.


From research findings to therapeutic opportunity:

The study presented here suggests, for the first time, that Glycine, by decreasing the expression of its target genes, it may increase PD-L1 levels (figs. 1-2). Thereby, it may: (a) inhibit acute and chronic pain; (b) alleviate thermal and mechanical hypersensitivity; (c) activate signal transduction cascade downstream of PD-1 receptor; (c) phosphorylate SHP-1; (d) inhibit sodium channels and nociceptive neuron excitability.

Figure 1.Mechanistic insights into how Glycine inhibits acute and chronic pain. Glycine enhances PD-L1 levels, suppresses thermal and mechanical hypersensitivity, phosphorylates SHP-1, inhibits activation of sodium channels, and alleviates nociceptive neuron excitability

Thus, pharmacological formulations encompassing Glycine or its analogues, either alone in combination with other drugs,” may be used to attenuate short-term and long-term pain.


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $500#

Undisclosed mechanistic information: How Glycine increases the expression of PD-L1 and attenuates pain.

# Research cooperation


References:

Citation: Boominathan, L., Activation of the PD-1 pathway for Pain therapy: Glycine, a non-essential amino acid and  neurotransmitter, increases the expression of PD-L1, attenuates acutes and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability via up-regulation of its target gene, 1/December/2017, 12.36 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscovery.org or http://newbioideas.com

Courtesy: When you cite drop us a line at info@genomediscovery.org

Comments are closed.