TY - JOUR
T1 - Mechanisms targeting the unfolded protein response in asthma
AU - Dastghaib, Sanaz
AU - Kumar, P. Sravan
AU - Aftabi, Sajjad
AU - Damera, Gautam
AU - Dalvand, Azadeh
AU - Sepanjnia, Adel
AU - Kiumarsi, Mohammad
AU - Aghanoori, Mohamad Reza
AU - Sohal, Sukhwinder Singh
AU - Ande, Sudharsana R.
AU - Alizadeh, Javad
AU - Mokarram, Pooneh
AU - Ghavami, Saeid
AU - Sharma, Pawan
AU - Zeki, Amir A.
N1 - Funding Information:
Supported by University of California, Davis, Principal Investigator Bridge Fund (A.A.Z.), the Rebecca Cooper Research Foundation (P.S. and S.S.S.), and a Research Manitoba New Investigator Operating grant (S.G.).
PY - 2021/1
Y1 - 2021/1
N2 - Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER), resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs. Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions, such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Furthermore, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Furthermore, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage. We also present an overview of the pathogenic mechanisms, with a brief focus on potential strategies for pharmacological interventions.
AB - Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER), resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs. Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions, such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Furthermore, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Furthermore, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage. We also present an overview of the pathogenic mechanisms, with a brief focus on potential strategies for pharmacological interventions.
KW - Asthma
KW - Endoplasmic reticulum
KW - Endoplasmic reticulum stress
KW - Unfolded protein response
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U2 - 10.1165/rcmb.2019-0235TR
DO - 10.1165/rcmb.2019-0235TR
M3 - Review article
C2 - 32915643
AN - SCOPUS:85098622738
VL - 64
SP - 29
EP - 38
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 1
ER -