scholarly journals MANF: A Novel Endoplasmic Reticulum Stress Response Protein—The Role in Neurological and Metabolic Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yang Yu ◽  
Dan-yang Liu ◽  
Xue-shen Chen ◽  
Ling Zhu ◽  
Li-hong Wan
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Metabolic Disorders ◽  
Early Stage ◽  
Disease Diagnosis ◽  
Endoplasmic Reticulum Stress Response ◽  
Unfolded Protein ◽  
Potential Applications ◽  
Protein Response

The mesencephalic astrocyte-derived neurotrophic factor (MANF), also named as arginine-rich protein (ARP) or arginine-rich mutated in early-stage tumors (ARMET), is a novel evolutionary conserved protein related to unfolded protein response. Growing evidence suggests that MANF critically involves in many ER stress-related diseases with a protective effect. Here, we review the function of MANF based on its structure in neurological and metabolic disorders and summarize its potential applications in disease diagnosis and therapies.

scholarly journals Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1442
Author(s):  
Lena Krammes ◽  
Martin Hart ◽  
Stefanie Rheinheimer ◽  
Caroline Diener ◽  
Jennifer Menegatti ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Neurodegenerative Disorders ◽  
Endoplasmic Reticulum Stress Response ◽  
Caspase Activity ◽  
Therapeutic Approaches ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration.

scholarly journals The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling

2021 ◽  
Author(s):  
Kashi Raj Bhattarai ◽  
Thoufiqul Alam Riaz ◽  
Hyung-Ryong Kim ◽  
Han-Jung Chae
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Stress Response ◽  
Er Stress ◽  
Protein Modification ◽  
Endoplasmic Reticulum Stress Response ◽  
Unfolded Protein ◽  
Er Stress Response ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractThe endoplasmic reticulum (ER) is an essential organelle of eukaryotic cells. Its main functions include protein synthesis, proper protein folding, protein modification, and the transportation of synthesized proteins. Any perturbations in ER function, such as increased demand for protein folding or the accumulation of unfolded or misfolded proteins in the ER lumen, lead to a stress response called the unfolded protein response (UPR). The primary aim of the UPR is to restore cellular homeostasis; however, it triggers apoptotic signaling during prolonged stress. The core mechanisms of the ER stress response, the failure to respond to cellular stress, and the final fate of the cell are not yet clear. Here, we discuss cellular fate during ER stress, cross talk between the ER and mitochondria and its significance, and conditions that can trigger ER stress response failure. We also describe how the redox environment affects the ER stress response, and vice versa, and the aftermath of the ER stress response, integrating a discussion on redox imbalance-induced ER stress response failure progressing to cell death and dynamic pathophysiological changes.

An update on lipotoxic endoplasmic reticulum stress in pancreatic β-cells

2008 ◽  
Vol 36 (5) ◽  
pp. 909-915 ◽  
Author(s):  
Miriam Cnop ◽  
Mariana Igoillo-Esteve ◽  
Daniel A. Cunha ◽  
Laurence Ladrière ◽  
Décio L. Eizirik
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Endoplasmic Reticulum Stress Response ◽  
Cell Recovery ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peripheral Tissues ◽  
Unfolded Protein

The UPR (unfolded protein response) or ER (endoplasmic reticulum) stress response was first described 20 years ago. The field of ER stress has expanded tremendously since, moving from basic biology in yeast to human neurodegenerative, inflammatory, cardiovascular and neoplastic diseases. The ER stress response has also been implicated in diabetes development, affecting both insulin production by pancreatic β-cells and insulin sensitivity in peripheral tissues. In the present mini-review, we focus on recent progress in the field of ER stress in pancreatic β-cells. Recent advances in the understanding of lipotoxic ER stress and β-cell recovery from ER stress are discussed.

scholarly journals Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7–dependent

2015 ◽  
Vol 112 (45) ◽  
pp. 14090-14095 ◽  
Author(s):  
Chandrashekara Kyathanahalli ◽  
Kenna Organ ◽  
Rebecca S. Moreci ◽  
Prashanth Anamthathmakula ◽  
Sonia S. Hassan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Unfolded Protein Response ◽  
Caspase 3 ◽  
Endoplasmic Reticulum Stress Response ◽  
Gestational Length ◽  
Unfolded Protein ◽  
Junction Protein ◽  
Protein Response

We previously identified myometrial caspase-3 (CASP3) as a potential regulator of uterine quiescence. We also determined that during pregnancy, the functional activation of uterine CASP3 is likely governed by an integrated endoplasmic reticulum stress response (ERSR) and is consequently limited by an increased unfolded protein response (UPR). The present study examined the functional relevance of uterine UPR-ERSR in maintaining myometrial quiescence and regulating the timing of parturition. In vitro analysis of the human uterine myocyte hTERT-HM cell line revealed that tunicamycin (TM)-induced ERSR modified uterine myocyte contractile responsiveness. Accordingly, alteration of in vivo uterine UPR-ERSR using a pregnant mouse model significantly modified gestational length. We determined that “normal” gestational activation of the ERSR-induced CASP3 and caspase 7 (CASP7) maintains uterine quiescence through previously unidentified proteolytic targeting of the gap junction protein, alpha 1(GJA1); however, surprisingly, TM-induced uterine ERSR triggered an exaggerated UPR that eliminated uterine CASP3 and 7 tocolytic action precociously. These events allowed for a premature increase in myometrial GJA1 levels, elevated contractile responsiveness, and the onset of preterm labor. Importantly, a successful reversal of the magnified ERSR-induced preterm birth phenotype could be achieved by pretreatment with 4-phenylbutrate, a chaperone protein mimic.

scholarly journals Activation of ATF6 and an ATF6 DNA Binding Site by the Endoplasmic Reticulum Stress Response

2000 ◽  
Vol 275 (35) ◽  
pp. 27013-27020
Author(s):  
Yan Wang ◽  
Jingshi Shen ◽  
Natalia Arenzana ◽  
Witoon Tirasophon ◽  
Randal J. Kaufman ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Dna Binding ◽  
Endoplasmic Reticulum Stress ◽  
Binding Site ◽  
Endoplasmic Reticulum Stress Response ◽  
Dna Binding Site
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