title: Unraveling the role of ER stress inhibitors in the context of metabolic diseases.
abstract: ER stress is provoked by the accumulation of unfolded and misfolded proteins in the ER lumen leading to perturbations in ER homeostasis. ER stress activates a signaling cascade called the Unfolded Protein Response (UPR) which triggers a set of transcriptional and translational events that restore ER homeostasis, promoting cell survival and adaptation. If this adaptive response fails, a terminal UPR program commits such cells to apoptosis. Existing preclinical and clinical evidence testify that prolonged ER stress escalates the risk of several metabolic disorders including diabetes, obesity and dyslipidemia. There have been considerable efforts to develop small molecules that are capable of ameliorating ER stress. Few naturally occurring and synthetic molecules have already been demonstrated for their efficacy in abrogating ER stress in both in vitro and in vivo models of metabolic disorders. This review provides a broad overview of the molecular mechanisms of inhibition of ER stress and its association with various metabolic diseases.
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India.
authors.forename: Chodisetty
authors.initials: C
authors.lastname: Sarvani
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India.
authors.forename: Dornadula
authors.initials: D
authors.lastname: Sireesh
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India. Electronic address: ramkumar.km@res.srmuniv.ac.in.
authors.forename: Kunka Mohanram
authors.initials: KM
authors.lastname: Ramkumar
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D055808:Drug Discovery / Q000379:methods; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*; D056811:Unfolded Protein Response / Q000187:drug effects; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D004722:Endoribonucleases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D054852:Small Molecule Libraries; D019892:eIF-2 Kinase; C497111:ATF6 protein, human; C528229:ERN1 protein, human
keywords: Diabetes; ER stress; ER stress inhibitors; Lipid disorders; Metabolic diseases; Obesity