Understanding the origin of non-immune cell-mediated weakness in the idiopathic inflammatory myopathies - potential role of ER stress pathways

Current Opinion in Rheumatology
Adam P LightfootRobert G Cooper

Abstract

Discussion of endoplasmic reticulum (ER) stress pathway activation in idiopathic inflammatory myopathies (IIM), and downstream mechanisms causative of muscle weakness. In IIM, ER stress is an important pathogenic process, but how it causes muscle dysfunction is unknown. We discuss relevant pathways modified in response to ER stress in IIM: reactive oxygen species (ROS) generation and mitochondrial dysfunction, and muscle cytokine (myokine) generation. First, ER stress pathway activation can induce changes in mitochondrial bioenergetics and ROS production. ROS can oxidize cellular components, causing muscle contractile dysfunction and energy deficits. Novel compounds targeting ROS generation and/or mitochondrial dysfunction can improve muscle function in several myopathologies. Second, recent research has demonstrated that skeletal muscle produces multiple myokines. It is suggested that these play a role in causing muscle weakness. Myokines are capable of immune cell recruitment, thus contributing to perturbed muscle function. A characterization of myokines in IIM would clarify their pathogenic role, and so identify new therapeutic targets. ER stress pathway activation is clearly of etiological relevance in IIM. Research to bett...Continue Reading

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Citations

Feb 24, 2016·Free Radical Biology & Medicine·Mario OstSusanne Klaus
Feb 13, 2016·Arthritis & Rheumatology·Adam P Lightfoot, Robert G Cooper
Apr 5, 2017·Journal of Immunoassay & Immunochemistry·Emilia ManoleHans H Goebel
Apr 21, 2018·Nature Reviews. Rheumatology·Frederick W MillerKanneboyina Nagaraju
Aug 6, 2016·Therapeutic Advances in Musculoskeletal Disease·James LillekerRobert Cooper
Aug 23, 2016·Current Opinion in Rheumatology·Adam P Lightfoot, Robert G Cooper
Sep 6, 2020·Current Opinion in Rheumatology·Marta Loredo MartinezMariele Gatto
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Jun 6, 2018·Journal of Neuromuscular Diseases·Jens Schmidt
Jan 19, 2019·Advances in Rheumatology·Diego Sales de OliveiraSamuel Katsuyuki Shinjo
Jun 13, 2020·BMC Rheumatology·Joanna E ParkesJanine A Lamb
Aug 4, 2016·The International Journal of Neuroscience·Zhibo ChenXu Zhang
Apr 2, 2021·International Journal of Rheumatic Diseases·Ilke Coskun Benlidayi, Latika Gupta

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Methods Mentioned

BETA
biopsies
protein folding
biopsy

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