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

Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

10.9K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
10.9K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

13.6K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.6K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

3.9K
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...
3.9K
Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

7.8K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
7.8K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

4.6K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.6K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

5.1K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
5.1K

You might also read

Related Articles

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

Sort by
Same author

Fluorothiazynes as SuFEx Ambiphiles: Interconversion to Amino-sulfurdiimidoyl Fluorides.

Angewandte Chemie (International ed. in English)·2025
Same author

Mixed Alkyl Aryl Phosphonates as Quenched Activity-Based Probes for Real-Time Imaging of Active Neutrophil Serine Proteases.

ACS chemical biology·2025
Same author

BDH2-driven lysosome-to-mitochondria iron transfer shapes ferroptosis vulnerability of the melanoma cell states.

Nature metabolism·2025
Same author

Sulfoxide-diazirine (SODA) as a Cleavable Photoaffinity Group To Enable the Identification of Photolabeled Modification Sites via LC-MS<sup>3</sup>.

Analytical chemistry·2025
Same author

Icosapent ethyl reduces arterial thrombosis by inhibition of cyclooxygenase-1-induced platelet reactivity.

Science translational medicine·2025
Same author

Polyamine depletion limits progression of acute leukaemia.

International journal of cancer·2025

Related Experiment Video

Updated: Mar 11, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

11.5K

Intramembrane proteases as drug targets.

Steven H L Verhelst1,2

  • 1Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, Belgium.

The FEBS Journal
|November 28, 2016
PubMed
Summary

Intramembrane proteases (IMPs) are crucial drug targets involved in diseases like Alzheimer's and cancer. While inhibitors exist, improving their potency and selectivity is key for developing new IMP-targeted therapies.

Keywords:
drug developmentgamma-secretaseintramembrane proteaseprotease inhibitorprotease modulatorproteolysisrhomboid proteasesignal peptide peptidasesite-2 protease

More Related Videos

Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
10:50

Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics

Published on: July 16, 2018

17.0K
Use of Recombinant Fusion Proteins in a Fluorescent Protease Assay Platform and Their In-gel Renaturation
19:23

Use of Recombinant Fusion Proteins in a Fluorescent Protease Assay Platform and Their In-gel Renaturation

Published on: January 16, 2019

9.8K

Related Experiment Videos

Last Updated: Mar 11, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

11.5K
Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
10:50

Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics

Published on: July 16, 2018

17.0K
Use of Recombinant Fusion Proteins in a Fluorescent Protease Assay Platform and Their In-gel Renaturation
19:23

Use of Recombinant Fusion Proteins in a Fluorescent Protease Assay Platform and Their In-gel Renaturation

Published on: January 16, 2019

9.8K

Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • Proteases are validated drug targets, with approved therapies for soluble forms.
  • Intramembrane proteases (IMPs) are membrane-embedded enzymes implicated in various human diseases.
  • Despite disease links, no IMP-targeting drugs are currently on the market.

Purpose of the Study:

  • To review the function of IMPs, emphasizing their role in human pathologies.
  • To discuss the current landscape of IMP inhibitors, including their limitations.
  • To identify challenges and future directions for IMP-directed drug development.

Main Methods:

  • Literature review of IMP functions and disease associations.
  • Analysis of existing IMP inhibitor classes and their characteristics.
  • Discussion of drug development hurdles and potential solutions.

Main Results:

  • IMPs are implicated in Alzheimer's disease, cancer, and infectious diseases.
  • Inhibitors are available for all IMP mechanistic classes, but generally lack potency and selectivity.
  • γ-secretase inhibitors represent a notable exception with some clinical success.

Conclusions:

  • IMPs represent a promising, yet challenging, class of drug targets.
  • Further research is needed to enhance the potency and selectivity of IMP inhibitors.
  • Addressing current limitations is critical for advancing IMP-based therapeutics.