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

Amyloid Fibrils03:03

Amyloid Fibrils

11.7K
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,...
11.7K
Parkinson's Disease: Overview01:15

Parkinson's Disease: Overview

1.8K
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
1.8K

You might also read

Related Articles

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

Sort by
Same author

Protocol for automated analysis of oil red O-stained Caenorhabditis elegans using Redwormpix, a Python-based application.

STAR protocols·2026
Same author

<i>C9orf72</i> -associated G4C2 hexanucleotide repeat expression in <i>Drosophila</i> mushroom bodies causes age dependent TDP-43 pathology and dementia relevant phenotypes mediated in part by the glypican Dlp/GPC6.

bioRxiv : the preprint server for biology·2026
Same author

The World Federation of Neurology Specialty Group in ALS/MND: toward strategic partnership and new frontiers.

Amyotrophic lateral sclerosis & frontotemporal degeneration·2026
Same author

MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) regulates long-range alternative splicing in Drosophila.

Nucleic acids research·2026
Same author

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis.

Nature metabolism·2026
Same author

Characterization of a C9orf72 Knockout Danio rerio model for ALS and cross-species validation of potential therapeutics screened in Caenorhabditis elegans.

PloS one·2026

Related Experiment Video

Updated: Jan 17, 2026

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
08:59

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Published on: July 16, 2021

3.1K

Protein Assembly Modulation: A New Approach to Amyotrophic Lateral Sclerosis (ALS) Therapeutics.

Shao Feng Yu1, Kumar Paulvannan1, Dennis Solas1

  • 1Prosetta Biosciences, Inc. 670 5th St San Francisco, CA 94107, USA.

Journal of Experimental Neurology
|September 22, 2025
PubMed
Summary
This summary is machine-generated.

Researchers discovered a novel small molecule targeting protein disulfide isomerase (PDI) in a protein complex, offering a new mechanism for Amyotrophic Lateral Sclerosis (ALS) pathogenesis. This compound shows promise in various ALS models, potentially revealing new therapeutic insights.

Keywords:
Affinity chromatographyAllosteryMolecular neuroscienceNeuro-degenerationPhenotypic screenPhotocrosslinkingProtein assemblySmall molecule drug discoveryStructure activity relationshipTranslational neuroscience

More Related Videos

Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
06:51

Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents

Published on: August 10, 2018

8.1K
ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
15:48

ALS - Motor Neuron Disease: Mechanism and Development of New Therapies

Published on: July 29, 2007

10.0K

Related Experiment Videos

Last Updated: Jan 17, 2026

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
08:59

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Published on: July 16, 2021

3.1K
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
06:51

Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents

Published on: August 10, 2018

8.1K
ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
15:48

ALS - Motor Neuron Disease: Mechanism and Development of New Therapies

Published on: July 29, 2007

10.0K

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Drug Discovery

Background:

  • Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron death.
  • Its pathophysiology is complex and multifactorial, with current understanding still evolving.

Purpose of the Study:

  • To introduce a novel mechanism of ALS pathogenesis.
  • To investigate a new drug-like small molecule series targeting protein disulfide isomerase (PDI).

Main Methods:

  • Phenotypic screening to identify a novel small molecule.
  • Testing the compound in cellular and transgenic animal models of ALS (worms, flies, mice).
  • Affinity chromatography to identify the drug target.

Main Results:

  • The identified small molecule demonstrated activity in cellular models for both familial and sporadic ALS.
  • The compound was effective in transgenic models carrying diverse human ALS-associated mutations.
  • Structure-activity relationship (SAR) optimization led to separation of HIV and ALS activities, and target identification.

Conclusions:

  • A novel drug-like small molecule targeting a specific PDI subset within a protein complex offers a new perspective on ALS pathogenesis.
  • This compound's efficacy across various ALS models suggests potential therapeutic value.
  • The findings may elucidate molecular mechanisms of disordered homeostasis relevant to ALS pathophysiology.