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Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein01:20

Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein

Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...

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Related Experiment Video

Updated: May 10, 2026

Quantitative Measurement of γ-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

γ-Secretase inhibitors and modulators.

Todd E Golde1, Edward H Koo, Kevin M Felsenstein

  • 1Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Biochimica Et Biophysica Acta
|June 25, 2013
PubMed
Summary

γ-Secretase inhibitors (GSIs) and modulators (GSMs) are investigated for Alzheimer's disease (AD) and cancer. While GSIs show promise, toxicity concerns necessitate careful benefit-risk evaluation for therapeutic use.

Keywords:
Alzheimer's diseaseCancerγ-Secretase inhibitorγ-Secretase modulator

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

Published on: January 25, 2018

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:

  • Biochemistry
  • Pharmacology
  • Neuroscience

Background:

  • γ-Secretase is a key intramembrane protease targeted for various diseases.
  • γ-Secretase inhibitors (GSIs) and modulators (GSMs) are under development for Alzheimer's disease (AD) and cancer.
  • Non-selective γ-secretase inhibition poses toxicity risks, requiring careful clinical evaluation.

Purpose of the Study:

  • To review the development status of GSIs and GSMs.
  • To explore biological and pharmacological questions regarding these agents.
  • To assess the therapeutic potential and risks of γ-secretase-targeting drugs.

Main Methods:

  • Review of preclinical and clinical studies on GSIs and GSMs.
  • Analysis of the mechanism of action for both GSIs and GSMs.
  • Investigation of γ-secretase substrate interactions beyond amyloid precursor protein (APP).

Main Results:

  • GSIs have been tested in human trials for AD and cancer, with potential in other conditions.
  • GSMs modulate γ-secretase activity, altering amyloid β (Aβ) peptide profiles.
  • Extensive investigation into GSMs' effects on non-APP substrates is lacking.

Conclusions:

  • GSIs offer therapeutic potential but require rigorous benefit-risk assessment due to toxicity.
  • GSMs present a potentially safer alternative, but their broader substrate effects need further study.
  • Continued research into γ-secretase modulators is crucial for developing safer AD therapeutics.