Related Experiment Video

Updated: Aug 14, 2026

Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Misfolded proteins, endoplasmic reticulum stress and neurodegeneration

Rammohan V Rao1, Dale E Bredesen

  • 1Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945-1400, USA. rrao@buckinstitute.org

Current Opinion in Cell Biology
|November 9, 2004
PubMed

Insights

Misfolded proteins trigger cellular stress, but prolonged buildup leads to cell death pathways. Understanding these pathways is key for treating neurodegenerative diseases caused by toxic protein accumulation.

Area of Science:

  • Cellular Biology
  • Neuroscience
  • Pathogenesis Research

Background:

  • Misfolded proteins, such as damaged or mutant proteins, accumulate within cells.
  • This accumulation triggers cellular stress responses to mitigate toxicity.
  • Prolonged cellular stress from protein buildup can initiate specific cell death pathways.

Purpose of the Study:

  • To investigate the cellular mechanisms underlying protein misfolding.
  • To elucidate the specific cell death pathways induced by prolonged protein stress.
  • To provide insights into the pathogenesis of neurodegenerative diseases.

Main Methods:

  • Analysis of cellular stress responses to misfolded proteins.
  • Identification and characterization of protein-induced cell death pathways.
  • Investigation of the role of these pathways in neurodegenerative disease models.

Main Results:

  • Cellular stress responses are activated by misfolded protein accumulation.
  • Sustained stress leads to the activation of distinct cell death pathways.
  • These pathways are implicated in the progression of diseases characterized by proteinopathies.

Conclusions:

  • Dissecting these specific cell death pathways is crucial.
  • Understanding these pathways offers therapeutic targets for neurodegenerative disorders.
  • This research aids in developing novel treatments for diseases involving protein misfolding.

More Related Videos

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans09:18

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans

Published on: September 7, 2021

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons10:50

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

Published on: April 24, 2021

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
The Unfolded Protein Response01:37

The Unfolded Protein Response

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...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...