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Published Online: 17 December 2015

Therapeutic Opportunities in Damage-Associated Molecular Pattern-Driven Metabolic Diseases

Publication: Antioxidants & Redox Signaling
Volume 23, Issue Number 17

Abstract

Significance: Sterile inflammation is a common finding present in various metabolic disorders. This type of inflammation is mediated by damage-associated molecular patterns (DAMPs) that are released upon cellular injury to activate pattern recognition receptors on innate immune cells and amplify organ damage. Recent Advances: In the last decade, DAMPs, such as high-mobility group protein B1, nucleic acids (DNA, RNA), adenosine triphosphate, and other metabolites, were found to contribute to the inflammatory response in diabetes, gout, obesity, steatohepatitis, and atherosclerosis. Varied receptors, including Toll-like receptors (TLRs), the purinergic P2X7 receptors, and nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3)-inflammasome sense DAMPs and DAMP-like molecules and release the proinflammatory cytokines, interleukin (IL)-1β and IL-18. Critical Issues: Available therapeutic approaches that interfered with the signaling of TLRs, P2X7, NLRP3-inflammasome, and IL-1β showed encouraging results in metabolic diseases, which will be also highlighted in this review. Future Directions: It is important to understand the origination of DAMPs and how they contribute to the inflammatory response in metabolic disorders to develop selective and efficient therapeutics for intervention. Antioxid. Redox Signal. 23, 1305–1315.

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cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 23Issue Number 17December 10, 2015
Pages: 1305 - 1315
PubMed: 26055926

History

Published online: 17 December 2015
Published in print: December 10, 2015
Published ahead of print: 27 July 2015
Published ahead of production: 9 June 2015
Accepted: 24 May 2015
Received: 15 May 2015

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Irma Garcia-Martinez
Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut.
Mohamed E. Shaker
Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Wajahat Z. Mehal
Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut.

Notes

Address correspondence to:Dr. Wajahat Z. MehalSection of Digestive DiseasesDepartment of Internal MedicineYale University333 Cedar Street, 1080 LMPP.O. Box 208019New Haven, CT 06520-8019E-mail: [email protected]

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