TNF α signaling beholds thalidomide saga: A review of mechanistic role of TNF-α signaling under thalidomide

Syamantak Majumder, Sree Rama Chaitanya Sreedhara, Santanu Banerjee, Suvro Chatterjee

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

Tumor necrosis factor alpha (TNF-α) is a pleiotropic inflammatory cytokine. The cytokine possesses both growth stimulating properties and growth inhibitory processes*and it appears to have self regulatory properties as well. Agents like etanercept and infliximab showed beneficial effects against rheumatoid arthritis by modulationg TNF-α proteins*however*these agents are largely unable to penetrate the blood-brain barrier*which severely limits their use in different conditions. Thalidomide*an inhibitor of TNF-α protein synthesis is readily capable of crossing the blood-brain barrier and thus thalidomide and its analogs are excellent candidates for use in determining the potential value of anti-TNF-α therapies in a variety of diseases. Thalidomide blocks TNF-α expression by different possible mechanisms. Down regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)*an essential transcription factor for TNF and other cytokines under thalidomide treatment leads to reduction in the TNF-α expression. Additionally*myeloid differentiation factor 88 (MyD88)*an adapter protein regulates the expression of TNF under thalidomide treatment. Thalidomide treatment also leads to destruction of TNF-α mRNA thus*reducing the total expression of TNF-α protein. Thalidomide also targets reactive oxygen species (ROS) and α1- acid glycoprotein (AGP) to regulate TNF-α. In the present review*we discuss different possible mechanism that regulates TNF-α under thalidomide treatment. Additionally*we suggest novel strategies for the future targeting combination therapies of thalidomide and its analogs with different other anti-inflammatory drug to curb TNF-α associated diseases.

Original languageEnglish (US)
Pages (from-to)1456-1467
Number of pages12
JournalCurrent Topics in Medicinal Chemistry
Volume12
Issue number13
DOIs
StatePublished - Aug 9 2012
Externally publishedYes

Keywords

  • Cytokines
  • Inflammation
  • Myeloid differentiation factor 88
  • Nuclear factor kappa B
  • Thalidomide
  • Tumor necrosis factor-a

ASJC Scopus subject areas

  • Drug Discovery

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