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Related Concept Videos

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...
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...
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...
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...
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...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

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Related Experiment Video

Updated: Jun 27, 2026

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

Cathepsins B and L differentially regulate amyloid precursor protein processing.

Donna M Klein1, Kevin M Felsenstein, Douglas E Brenneman

  • 1Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, Spring House, Pennsylvania, USA. DKlein30@its.jnj.com

The Journal of Pharmacology and Experimental Therapeutics
|December 10, 2008
PubMed
Summary

Cathepsin B (catB) regulates amyloid beta (Abeta) release in neurons, potentially via a secretory pathway. Electrical activity and catB inhibition both reduce Abeta, suggesting a link in this novel APP processing pathway.

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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

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Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
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Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase

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Last Updated: Jun 27, 2026

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

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

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
11:57

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase

Published on: June 24, 2025

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Previous research indicates cathepsins influence amyloid beta (Abeta) levels in chromaffin cells through a regulated secretory pathway.
  • The role of cathepsins and electrical activity in Abeta release within primary hippocampal neurons remains to be fully elucidated.

Purpose of the Study:

  • To investigate the coregulation of Abeta release by cathepsins and electrical activity in primary hippocampal neurons.
  • To determine the specific roles of cathepsin B (catB) and cathepsin L (catL) in amyloid precursor protein (APP) processing and Abeta generation.

Main Methods:

  • Inhibition of catB using CA074Me and attenuation of catB expression via small interfering RNA.
  • Treatment with tetrodotoxin (TTX) to assess the link between catB-dependent Abeta release and electrical activity.
  • Pharmacological inhibition of catL and measurement of C-terminal fragments of APP to analyze secretase activity.

Main Results:

  • Inhibition of catB or suppression of beta-site APP-cleaving enzyme 1 (BACE1) expression decreased Abeta release.
  • No additive effect was observed between TTX and CA074Me treatments, indicating a connection between catB and electrical activity.
  • Inhibition of catL selectively increased Abeta42 levels, suggesting enhanced alpha-secretase activity and reduced overall Abeta42 generation.

Conclusions:

  • Evidence supports an alternative pathway for APP processing involving catB and activity-dependent Abeta release in a regulated secretory pathway for primary neurons.
  • Cathepsin B plays a significant role in regulating Abeta release, possibly through modulation of BACE1 activity.
  • Cathepsin L influences APP processing by affecting alpha-secretase activity, leading to altered Abeta42 levels.