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Cathepsin S Inhibition: Reducing Pain is the Mission
Author(s) -
Radler Shawn,
Lantzsch Maddie,
Finfrock Julie,
Hefferan Sarah,
Shimmin Bo,
Currier Kristopher,
Futch Liane,
Ondoua Alysia
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb254
Subject(s) - cats , microglia , neuropathic pain , cathepsin s , immune system , neuroscience , medicine , chronic pain , receptor , noxious stimulus , cysteine protease , nociceptor , nociception , cathepsin , pharmacology , inflammation , microbiology and biotechnology , immunology , chemistry , protease , biology , enzyme , biochemistry
Chronic pain results from continuous inflammatory and neuropathic pain affecting 116 million Americans with conditions such as rheumatoid arthritis and multiple sclerosis. Cathepsin_S (CatS), a lysosomal cysteine protease, an important mediator of pain, is released from antigen presenting cells such as microglia. Interactions between immune cells and neurons contribute to normal pain perception. Continuous noxious stimuli cause a local ATP increase, stimulating P2x7, a microglial receptor, to release CatS. CatS cleaves fractalkine (FKN), a neuronal transmembrane protein. Active FKN binds to its receptor, CX33CRI, on microglia, releasing inflammatory mediators that activate neighboring neurons and induce the perception of pain in the affected region. Competitive inhibitors of CatS have the potential to selectively attenuate the perception of pain as evidenced in animal models. The Ironwood Ridge High School SMART Team (Students Modeling A Research Topic) has modeled interactions between CatS and competitive inhibitors using 3D printing technology. Computer imaging of this site gives critical knowledge useful towards the development of a CatS specific inhibitor to treat pain clinically. Supported by a grant from NIH‐SEPA.