Mechanisms targeting the unfolded protein response in asthma

Sanaz Dastghaib, P. Sravan Kumar, Sajjad Aftabi, Gautam Damera, Azadeh Dalvand, Adel Sepanjnia, Mohammad Kiumarsi, Mohamad Reza Aghanoori, Sukhwinder Singh Sohal, Sudharsana R. Ande, Javad Alizadeh, Pooneh Mokarram, Saeid Ghavami, Pawan Sharma, Amir A. Zeki

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume64
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Asthma
  • Endoplasmic reticulum
  • Endoplasmic reticulum stress
  • Unfolded protein response

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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