Triggering receptor expressed on myeloid cells receptor family modulators: A patent review

Christopher J. Pelham, Amit N. Pandya, Devendra K. Agrawal

Research output: Contribution to journalReview article

20 Scopus citations

Abstract

Introduction: Triggering receptor expressed on myeloid cells (TREM) receptors and TREM-like transcript (TLT; or TREML) receptors of the immunoglobulin superfamily are known as key modulators of host immune responses. TREM-1 (CD354) and TREM-2 share the transmembrane adaptor DNAX-activation protein of 12 kDa (DAP12), but they possess separate stimulatory and inhibitory functional roles, especially in myeloid cells. Areas covered: This review covers findings related to TREMs and TLTs published in patent applications from their discovery in 2000 to the present. New roles for TREM-1, TREM-2, TLT-1 and TLT-2 in maladies ranging from acute and chronic inflammatory disorders to cardiovascular diseases and cancers are discussed. Putative endogenous ligands and novel synthetic peptide blockers are also discussed. Expert opinion: So far, therapeutic use of activators/blockers specific for TREMs and TLTs has been limited to preclinical animal models. TREM-1 is an immediate therapeutic target for acute and chronic inflammatory conditions, especially sepsis. Certain mutations in DAP12 and TREM-2 manifest into a disorder named polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, and newly identified TREM-2 variants confer a significant increase in risk of developing Alzheimer's disease. This makes TREM-2 an attractive therapeutic target for neurodegenerative diseases.

Original languageEnglish
Pages (from-to)1383-1395
Number of pages13
JournalExpert Opinion on Therapeutic Patents
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

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All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

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