Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The Unfolded Protein Response01:37

The Unfolded Protein Response

5.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.6K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

4.5K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.5K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.8K
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...
2.8K
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

6.3K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
6.3K
The Proteasome01:13

The Proteasome

1.3K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.3K
The Proteasome02:18

The Proteasome

9.3K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
9.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Protein disulfide isomerases in amyotrophic lateral sclerosis: Endoplasmic reticulum proteostasis and neuromuscular function.

Neural regeneration research·2026
Same author

Characterization of the mutational status of glioblastoma and high-grade astrocytomas in a Latin American cohort.

Scientific reports·2025
Same author

Proteostasis decline and endoplasmic reticulum stress in aging: Implications for cellular senescence and senescence-associated secretory phenotype regulation.

Neural regeneration research·2025
Same author

Expression of amyotrophic lateral sclerosis associated protein disulfide isomerase A3 D217N variant recapitulates early morphological alterations at the neuromuscular junction.

Neurobiology of disease·2025
Same author

Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders.

Biochemical Society transactions·2025
Same author

In Vivo Glioblastoma Tumor Modeling via Stereotaxic Injection in Mice for Tumor Progression Studies.

Journal of visualized experiments : JoVE·2025

Related Experiment Video

Updated: Nov 4, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.2K

Disruption of Endoplasmic Reticulum Proteostasis in Age-Related Nervous System Disorders.

Danilo B Medinas1,2,3, Younis Hazari4,5,6, Claudio Hetz7,8,9,10

  • 1Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. dmedinas@med.uchile.cl.

Progress in Molecular and Subcellular Biology
|May 29, 2021
PubMed
Summary

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in neurodegeneration. This review analyzes ER stress in human diseases and models, linking metabolic syndrome to neurodegeneration via ER stress.

Keywords:
AgingER stressMetabolic syndromeNeurodegenerative diseasesProtein misfolding

More Related Videos

Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
11:57

Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans

Published on: November 26, 2017

8.8K
Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
09:18

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans

Published on: September 7, 2021

3.1K

Related Experiment Videos

Last Updated: Nov 4, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.2K
Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
11:57

Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans

Published on: November 26, 2017

8.8K
Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
09:18

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans

Published on: September 7, 2021

3.1K

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Pathology

Background:

  • Endoplasmic reticulum (ER) stress, triggered by misfolded proteins, is central to aging-related neurodegenerative diseases.
  • The unfolded protein response (UPR) pathway adapts to ER stress but can also induce inflammation and cell death, leading to neurodegeneration.
  • Current research often uses models of familial neuropathies or toxin-induced pathology in young animals.

Purpose of the Study:

  • To systematically analyze the evidence linking ER stress to human pathology.
  • To review mechanisms of ER stress and UPR activation in experimental models.
  • To explore the role of ER stress in age-related sporadic neurodegenerative diseases and its connection to metabolic syndrome.

Main Methods:

  • Systematic literature review and analysis of existing evidence.
  • Examination of genetic and pharmacological studies in experimental models.
  • Integration of findings on ER stress, UPR, neurodegeneration, and metabolic syndrome.

Main Results:

  • ER stress is a significant factor in various nervous system diseases associated with protein aggregation.
  • UPR activation can be both adaptive and detrimental, contributing to neurodegeneration.
  • ER stress acts as a common pathway linking metabolic syndrome to an increased risk of neurodegeneration.

Conclusions:

  • Mechanisms identified in familial disease models may not fully represent sporadic, age-related neurodegenerative diseases.
  • ER stress is a critical link between peripheral metabolic dysfunction and central nervous system pathology.
  • Further research is needed to understand the relevance of ER stress in the majority of human neurodegenerative conditions.