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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...
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...
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...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
The Proteasome01:13

The Proteasome

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 (ubiquitin...
The Proteasome02:18

The Proteasome

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...

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Related Experiment Video

Updated: Jun 3, 2026

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
10:08

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

Regulated intramembrane proteolysis--lessons from amyloid precursor protein processing.

Stefan F Lichtenthaler1, Christian Haass, Harald Steiner

  • 1DZNE-German Center for Neurodegenerative Diseases, Adolf-Butenandt-Institute, Biochemistry, Ludwig-Maximilians-University, Munich, Germany.

Journal of Neurochemistry
|March 19, 2011
PubMed
Summary

Regulated intramembrane proteolysis (RIP) is a key cell signaling process. This review focuses on APP proteases, crucial for understanding Alzheimer's disease mechanisms.

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Rapid Generation of Amyloid from Native Proteins In vitro
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Rapid Generation of Amyloid from Native Proteins In vitro

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Related Experiment Videos

Last Updated: Jun 3, 2026

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
10:08

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Regulated intramembrane proteolysis (RIP) governs cell communication and is vital in the nervous system and other tissues.
  • RIP involves sequential cleavages of membrane proteins, releasing signaling fragments or enabling intracellular domain release.
  • Dysregulation of RIP is implicated in diseases like leukemia and Alzheimer's disease.

Purpose of the Study:

  • To review the function and mechanism of proteases involved in amyloid precursor protein (APP) regulated intramembrane proteolysis.
  • To elucidate the general cellular mechanisms and common principles of the RIP process, using APP as a model substrate.

Main Methods:

  • Literature review focusing on studies of APP processing and RIP proteases.
  • Analysis of the molecular mechanisms underlying RIP in the context of APP cleavage.

Main Results:

  • APP processing by RIP proteases generates amyloid-beta peptide, a key factor in Alzheimer's disease pathogenesis.
  • Identified APP as an early and well-studied substrate providing insights into RIP pathways.

Conclusions:

  • Understanding APP RIP proteases is critical for deciphering Alzheimer's disease mechanisms.
  • RIP is a fundamental biological process with broad implications across various cellular functions and diseases.