Related Experiment Video
Updated: Jun 13, 2026

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase
Published on: June 30, 2023
Fighting disease by selective autophagy of aggregate-prone proteins
Helene Knaevelsrud1, Anne Simonsen
1Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Abstract:
Ubiquitinated protein aggregates are hallmarks of a range of human diseases, including neurodegenerative, liver and muscle disorders. These protein aggregates are typically positive for the autophagy receptor p62. Whereas the ubiquitin-proteasome system (UPS) degrades shortlived and misfolded ubiquitinated proteins that are small enough to enter the narrow pore of the barrel-shaped proteasome, the lysosomal pathway of autophagy can degrade larger structures including entire organelles or protein aggregates. This degradation requires autophagy receptors that link the cargo with the molecular machinery of autophagy and is enhanced by certain posttranslational modifications of the cargo. In this review we focus on how autophagy clears aggregate-prone proteins and the relevance of this process to protein aggregate associated diseases.
Insights
Autophagy clears harmful protein aggregates linked to diseases like neurodegeneration. This process uses autophagy receptors to degrade these aggregates, offering therapeutic potential for protein aggregate disorders.
Area of Science:
- Cellular Biology
- Molecular Biology
- Pathology
Background:
- Ubiquitinated protein aggregates are implicated in various human diseases, including neurodegenerative, liver, and muscle disorders.
- These aggregates are often associated with the autophagy receptor p62.
- The ubiquitin-proteasome system (UPS) handles small proteins, while autophagy degrades larger structures like aggregates.
Purpose of the Study:
- To review the mechanisms by which autophagy clears aggregate-prone proteins.
- To discuss the significance of this autophagic clearance in protein aggregate-associated diseases.
Main Methods:
- Literature review focusing on autophagy, protein aggregation, and related diseases.
- Analysis of the roles of autophagy receptors and posttranslational modifications in cargo degradation.
Main Results:
- Autophagy is a key pathway for degrading large protein aggregates that the UPS cannot handle.
- Autophagy receptors are essential for linking protein aggregates to the autophagic machinery.
- Posttranslational modifications can enhance the clearance of aggregate-prone proteins by autophagy.
Conclusions:
- Autophagy plays a critical role in preventing the accumulation of toxic protein aggregates.
- Understanding autophagic clearance mechanisms is crucial for developing therapeutic strategies for protein aggregate diseases.
Related Concept Videos
The Proteasome
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 (ubiquitin...
The Proteasome
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...
Autophagy
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Delivery Pathways to the Lysosome
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Cellular Injury V: Apoptosis and Autophagy
Lysosomal Hydrolases

