Endoplasmic reticulum stress and inflammation in the central nervous system

Abstract

Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu. Nevertheless, there still remains a gap in knowledge regarding the cell-specific mechanisms by which ER stress mediates neuroinflammation. In this review, we will discuss recently uncovered inflammatory pathways linked to the ER stress response. Moreover, we will summarize the present literature delineating how ER stress is generated in Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis, and highlight how ER stress and neuroinflammation intersect mechanistically within the central nervous system. The mechanisms by which stress-induced inflammation contributes to the pathogenesis and progression of neurodegenerative diseases remain poorly understood. Further examination of this interplay could present unappreciated insights into the development of neurodegenerative diseases, and reveal new therapeutic targets.

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

“…Recent studies have suggested that endoplasmic reticulum stress (ERS) plays an essential role in inflammatory responses, and is involved in the pathological process of inflammatory diseases. 9,10 The ERS downstream pathway inositol-requiring kinase 1 (IRE1) regulates apoptosis via the ASK1-c-terminal kinase (JNK) pathway. 11 Therefore, ASK1 is correlated with ERS.…”

Macrophage migration inhibitory factor knockout attenuates endotoxin-induced cardiac dysfunction in mice

“…Our results revealed overt ER stress in the myocardium following LPS-induced endotoxaemia. ER stress has been shown to contribute to neurodegenerative disorders and ischaemia reperfusion-induced cardiac damage [21,22]. Our data revealed upregulated expression of the ER chaperone Grp78, which directly interacts with all three ER stress sensors, eIF2a, Gadd153, and IRE1a in sepsis.…”

Behçet Disease-Like Symptoms with a Novel COPA Mutation

“…Neuropathic symptoms in COPA syndrome have also not been widely reported previously; however, all three of the patients in this report manifested with various neural symptomatology. ER stress has been linked with central nervous system inflammation and neuronal dysfunction [16] and may be another aspect of the broader COPA syndrome phenotype.…”