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Regulation of the Unfolded Protein Response

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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

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Related Experiment Video

Updated: Jun 22, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

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The endoplasmic reticulum stress response and aging.

Nirinjini Naidoo¹

¹University of Pennsylvania School of Medicine, Center for Sleep and Respiratory Neurobiology, Philadelphia, PA 19104, USA. naidoo@mail.med.upenn.edu

Reviews in the Neurosciences

|June 17, 2009

Summary

Aging compromises the unfolded protein response (UPR), a key cellular stress pathway. This decline in UPR function may accelerate age-related neurodegenerative disorders.

Area of Science:

Cellular Biology
Neuroscience
Aging Research

Background:

The endoplasmic reticulum (ER) is vital for protein folding, lipid synthesis, and calcium homeostasis.
ER stress triggers the unfolded protein response (UPR) to restore cellular balance.
Aging is associated with reduced UPR efficiency and increased oxidative damage.

Purpose of the Study:

To investigate the impact of aging on the unfolded protein response (UPR).
To explore the link between impaired UPR and neurodegenerative disease progression.

Main Methods:

Review of existing literature on ER homeostasis, UPR, aging, and neurodegeneration.
Analysis of age-related changes in UPR component expression and activity.
Examination of evidence for oxidative damage in aging cells.

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Last Updated: Jun 22, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

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Published on: June 14, 2024

Measurements of Physiological Stress Responses in C. Elegans

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

Main Results:

UPR components show decreased expression and activity with advancing age.
Aging is characterized by significant oxidative damage.
An impaired UPR is implicated in the acceleration of neurodegenerative disorders.

Conclusions:

Aging impairs the adaptive capacity of the UPR.
Compromised UPR function in aging may contribute to neurodegeneration.
Further research into UPR modulation could offer therapeutic strategies for age-related neurological conditions.