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

Processes of Self-Presentation01:29

Processes of Self-Presentation

212
Effective self-presentation is a central component of social interaction and identity construction. It relies on the dynamic processes of defining the situation and engaging in self-disclosure. These mechanisms help individuals navigate social context expectations and manage how others perceive them, fostering mutual understanding and relationship development.Defining the SituationSocial situations are shaped by collectively understood frames—a set of widely understood rules or...
212
Information Processing Approach01:30

Information Processing Approach

538
The information-processing theory of cognitive development centers on fundamental mental processes, including attention, memory, and problem-solving skills. Researchers in this field examine how cognitive abilities, such as working memory, evolve and influence children's overall development. Studies indicate that children with stronger working memory tend to excel in reading comprehension, math, and problem-solving compared to peers with less efficient memory skills. Low working memory is...
538
Parallel Processing01:20

Parallel Processing

651
The brain processes sensory information rapidly due to parallel processing, which involves sending data across multiple neural pathways at the same time. This method allows the brain to manage various sensory qualities, such as shapes, colors, movements, and locations, all concurrently. For instance, when observing a forest landscape, the brain simultaneously processes the movement of leaves, the shapes of trees, the depth between them, and the various shades of green. This enables a quick and...
651
Precipitation Processes01:12

Precipitation Processes

5.8K
The experimental conditions in a gravimetric analysis should be optimized to maximize the particle size and purity of the obtained precipitate. Ideally, the concentration of the precipitating reagent should be low with effective stirring to maintain low relative supersaturation for the growth of large crystals. In homogeneous precipitation, the precipitant is slowly generated by a chemical reaction in the solution to avoid local reagent excesses. For example, urea decomposes gradually to...
5.8K
Isothermal Processes01:21

Isothermal Processes

4.9K
A thermodynamic process that occurs at constant temperature is called an isothermal process. Heat slowly flows into the system or out of the system to maintain thermal equilibrium. Processes involving phase changes like water evaporation into steam or freezing water into ice at a constant temperature are examples of Isothermal Processes.
An ideal gas can also undergo isothermal expansion or compression.
For example, consider 1 mole of an ideal gas inside an isolated cylinder at initial volume V...
4.9K
Work Done in an Adiabatic Process01:20

Work Done in an Adiabatic Process

4.2K
Consider the adiabatic compression of an ideal gas in the cylinder of an automobile diesel engine. The gasoline vapor is injected into the cylinder of an automobile engine when the piston is in its expanded position. The temperature, pressure, and volume of the resulting gas-air mixture are 20 °C, 1.00 x 105 N/m2, and 240 cm3 , respectively. The mixture is then compressed adiabatically to a volume of 40 cm3. Note that, in the actual operation of an automobile engine, the compression is not...
4.2K

You might also read

Related Articles

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

Sort by
Same author

The γ-secretase complex: from discovery to a therapeutic target.

RSC chemical biology·2026
Same author

A C. elegans model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.

Neurobiology of disease·2026
Same author

A <i>C. elegans</i> model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.

bioRxiv : the preprint server for biology·2025
Same author

Presenilin-1 Familial Alzheimer Mutations Impair γ-Secretase Cleavage of APP Through Stabilized Enzyme-Substrate Complex Formation.

Biomolecules·2025
Same author

γ-Secretase-Mediated Endoproteolysis of Neuregulin-1 and E-Cadherin.

Biochemistry·2025
Same author

Presenilin, γ-Secretase, and the Search for Pathogenic Triggers of Alzheimer's Disease.

Biochemistry·2025
Same journal

Effect of Ca<sup>2+</sup> and Mg<sup>2+</sup> on the conformational dynamics of membrane-anchored Bcl-xL.

Biochimica et biophysica acta. Biomembranes·2026
Same journal

Compositional analysis and functional insights of the cell envelope in Synechocystis sp. PCC 6803.

Biochimica et biophysica acta. Biomembranes·2026
Same journal

From membrane disruption to intracellular targets: A solid-state NMR perspective on antimicrobial peptide mechanism.

Biochimica et biophysica acta. Biomembranes·2026
Same journal

The human adenosine A<sub>2A</sub> receptor co-isolates with anionic phospholipids in SMALPs from Pichia pastoris membranes.

Biochimica et biophysica acta. Biomembranes·2026
Same journal

Collective lipid dynamics in biomembranes.

Biochimica et biophysica acta. Biomembranes·2026
Same journal

Exposure to the antimicrobial peptides LL-37 and ATRA-1 induces a lipidome response in Staphylococcus aureus that alters membrane biophysical properties.

Biochimica et biophysica acta. Biomembranes·2026
See all related articles

Related Experiment Video

Updated: Jan 22, 2026

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by &#947;-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

527

Substrate recognition and processing by γ-secretase.

Michael S Wolfe1

  • 1Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66045, USA.

Biochimica Et Biophysica Acta. Biomembranes
|July 12, 2019
PubMed
Summary
This summary is machine-generated.

The γ-secretase enzyme cleaves membrane proteins like amyloid precursor protein, crucial for Alzheimer's disease research. New findings reveal how it recognizes substrates and its active site pockets guide precise protein cutting.

Keywords:
Alzheimer's diseaseAmyloidBiochemistryGeneticsNotchProtease

More Related Videos

Quantitative Measurement of &#947;-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
06:40

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms

Published on: January 25, 2018

7.1K
Interaction between Phonological and Semantic Processes in Visual Word Recognition using Electrophysiology
05:38

Interaction between Phonological and Semantic Processes in Visual Word Recognition using Electrophysiology

Published on: June 29, 2021

2.8K

Related Experiment Videos

Last Updated: Jan 22, 2026

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by &#947;-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

527
Quantitative Measurement of &#947;-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
06:40

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms

Published on: January 25, 2018

7.1K
Interaction between Phonological and Semantic Processes in Visual Word Recognition using Electrophysiology
05:38

Interaction between Phonological and Semantic Processes in Visual Word Recognition using Electrophysiology

Published on: June 29, 2021

2.8K

Area of Science:

  • Molecular Biophysics
  • Membrane Protein Biochemistry
  • Neuroscience

Background:

  • The γ-secretase complex is a crucial enzyme involved in cleaving numerous type I integral membrane proteins.
  • Key substrates include Notch receptors and amyloid precursor protein (APP), with implications for cell differentiation and Alzheimer's disease pathogenesis.
  • Understanding γ-secretase's mechanism is vital for therapeutic development.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying γ-secretase substrate recognition and processive proteolysis.
  • To investigate the roles of specific subunits and active site features in enzyme function.
  • To provide insights into how Alzheimer's-associated mutations affect γ-secretase activity.

Main Methods:

  • Review of recent findings on γ-secretase substrate processing.
  • Analysis of the role of nicastrin in substrate recognition.
  • Examination of presenilin mutations and their impact on APP cleavage.
  • Biophysical characterization of active site pockets.

Main Results:

  • Nicastrin acts as a gatekeeper, influencing substrate recognition by γ-secretase.
  • Presenilin mutations linked to Alzheimer's disease alter the processive proteolysis of APP.
  • Evidence suggests three active site pockets (S1", S2", S3") dictate carboxypeptidase cleavage at three-residue intervals.

Conclusions:

  • γ-secretase employs a sophisticated mechanism involving substrate recognition and precise cleavage guided by its active site structure.
  • These findings advance our understanding of membrane protein processing and its link to neurodegenerative diseases.
  • The detailed mechanistic insights could inform future therapeutic strategies targeting γ-secretase activity.