Mechanisms Targeting the Unfolded Protein Response in Asthma.
Sanaz DastghaibP Sravan KumarSajjad AftabiGautam DameraAzadeh DalvandAdel SepanjniaMohammad KiumarsiMohamad-Reza AghanooriSukhwinder Singh SohalSudharsana R AndeJavad AlizadehPooneh MokarramSaeid GhavmiPawan SharmaAmir A ZekiPublished in: American journal of respiratory cell and molecular biology (2021)
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.
Keyphrases
- endoplasmic reticulum
- induced apoptosis
- metabolic syndrome
- signaling pathway
- protein protein
- oxidative stress
- endoplasmic reticulum stress
- cell cycle arrest
- chronic obstructive pulmonary disease
- amino acid
- endothelial cells
- binding protein
- squamous cell carcinoma
- type diabetes
- cell therapy
- cell death
- pi k akt
- risk assessment
- cardiovascular disease
- young adults
- estrogen receptor
- insulin resistance
- current status
- cardiovascular risk factors
- lymph node metastasis
- induced pluripotent stem cells
- childhood cancer