Endoplasmic Reticulum Stress and Its Role in Homeostasis and Immunity of Central and Peripheral Neurons

Abstract

Neuronal cells are specialists for rapid transfer and translation of information. Their electrical properties relay on a precise regulation of ion levels while their communicationvianeurotransmitters and neuropeptides depends on a high protein and lipid turnover. The endoplasmic Reticulum (ER) is fundamental to provide these necessary requirements for optimal neuronal function. Accumulation of misfolded proteins in the ER lumen, reactive oxygen species and exogenous stimulants like infections, chemical irritants and mechanical harm can induce ER stress, often followed by an ER stress response to reinstate cellular homeostasis. Imbedded between glial-, endothelial-, stromal-, and immune cells neurons are constantly in communication and influenced by their local environment. In this review, we discuss concepts of tissue homeostasis and innate immunity in the central and peripheral nervous system with a focus on its influence on ER stress, the unfolded protein response, and implications for health and disease.

Potential Crosstalk between the PACAP/VIP Neuropeptide System and Endoplasmic Reticulum Stress—Relevance to Multiple Sclerosis Pathophysiology

“…Based on the evidence provided, there is strong potential to eliminate the exacerbated and chronic activation of resident and peripheral immune cells by suppressing ER stress in immune cells [107]. This could include dampening ER stress triggers via the modulation of calcium signaling, inhibiting ER stress responses by tackling specific branches of the UPR such as XBP1 or IRE1α kinase, or by implementing antioxidative strategies [107,108]. Such activities seem to be regulated by the PACAP/VIP system (summarized in Figure 2).…”

High glucose-induced imbalance of mitochondria-associated ER membranes function promotes RSC96 cell damage

“…With the intensive study of cellular ultrastructure, the structural functions and related roles of mitochondria and endoplasmic reticulum have shown to be important in many diseases (5,6) Mitochondrial-related ER membranes (MAMs), a newly discovered subcellular structure, abnormalities in the function and structure of MAMs are closely associated with the development of neurological diseases (7,8). MAMs are composed of multiple functional protein molecules and mediate functional effects, including mitofusin-2 (Mfn2), protein kinase R (PKR) like ER kinase (PERK), voltage-dependent anion channel 1 (VDAC1), inositol 1.…”

Ischemic preconditioning attenuates ERS-dependent apoptosis of hepatocyte through regulating autophagy in hepatic ischemia reperfusion injury

“…It plays a vital role in maintaining the intracellular homeostasis. Endoplasmic reticulum controls the correct modi cation and folding of three-dimensional structure of proteins [14].…”