The effect of statin therapy on endoplasmic reticulum stress

Hamid Mollazadeh, Stephen Atkin, Alexandra E. Butler, Massimiliao Ruscica, Cesare R. Sirtori, Amirhossein Sahebkar

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) is critical in protein processing and particularly in ensuring that proteins undergo their correct folding to exert their functionality. What is becoming increasingly clear is that the ER may undergo increasing stress brought about by nutrient deprivation, hypoxia, oxidized lipids, point mutations in secreted proteins, cellular differentiation or significant deviation from metabolic set points, and loss of Ca2+ homeostasis, with detrimental effects on ER-resident calcium-dependent chaperones, alone or in combination. This results in the unfolded protein response (UPR) that is a repair mechanism to limit the formation of newly damaged proteins until ER homeostasis is restored, though may result in increased cell death. ER stress has been shown to be implicated in a variety of diseases. Statins are well-known cholesterol-lowering drugs and have been extensively reported to possess beneficial cholesterol-independent effects in a variety of human diseases. This review focuses on the concept of ER stress, the underlying molecular mechanisms and their relationship to the pathophysiology and, finally, the role of statins in moderating ER stress and UPR.

Original languageEnglish
Pages (from-to)150-158
Number of pages9
JournalPharmacological Research
Volume137
DOIs
Publication statusPublished - 1 Nov 2018

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Keywords

  • Endoplasmic reticulum stress
  • Pleiotropic effect
  • Statins
  • Unfolded protein response

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mollazadeh, H., Atkin, S., Butler, A. E., Ruscica, M., Sirtori, C. R., & Sahebkar, A. (2018). The effect of statin therapy on endoplasmic reticulum stress. Pharmacological Research, 137, 150-158. https://doi.org/10.1016/j.phrs.2018.10.006