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 Experiment Videos

BACE1 suppression by RNA interference in primary cortical neurons.

Shih-Chu Kao1, Anna M Krichevsky, Kenneth S Kosik

  • 1Department of Pathology, Harvard Medical School and Howard Hughes Medical Institute, Armenise Building, 200 Longwood Avenue, Boston, MA 02115, USA.

The Journal of Biological Chemistry
|November 6, 2003
PubMed
Summary

Small interfering RNA (siRNA) targeting beta-secretase 1 (BACE1) effectively reduces amyloid-beta (Abeta) production in Alzheimer's disease models. This BACE1 siRNA approach also mitigated neurotoxicity, suggesting therapeutic potential for Alzheimer's disease.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

A wireless subdural-contained brain-computer interface with 65,536 electrodes and 1,024 channels.

Nature electronics·2026
Same author

High-Throughput Screening Identifies Small-Molecule Inhibitors of the Tau-LRP1 Interaction.

bioRxiv : the preprint server for biology·2026
Same author

tRNA-derived fragments are elevated in the aging brain and may contribute to neurodegeneration.

bioRxiv : the preprint server for biology·2026
Same author

tRNA-derived fragments elevated in Alzheimer's disease facilitate Tau aggregation.

bioRxiv : the preprint server for biology·2026
Same author

Genetic modifiers in autosomal dominant Alzheimer's disease.

The Lancet. Neurology·2026
Same author

BAG2 Condensates Couple Proteostasis to CD8<sup>+</sup>T Cell Surveillance.

bioRxiv : the preprint server for biology·2026

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta) aggregates in the brain.
  • Abeta peptides originate from amyloid precursor proteins (APPs) cleaved by beta- and gamma-secretases.
  • Beta-secretase 1 (BACE1) initiates Abeta generation by cleaving APP, making it a therapeutic target for AD.

Purpose of the Study:

  • To investigate the efficacy of small interfering RNA (siRNA) targeting BACE1 to suppress its expression and Abeta production.
  • To evaluate the therapeutic potential of BACE1 siRNA in cellular models of Alzheimer's disease.

Main Methods:

  • Utilized small interfering RNA (siRNA) specifically designed to target BACE1 in various cell systems.
  • Assessed BACE1 protein expression levels and its impact on APP beta-cleaved C-terminal fragments (betaCTF) and Abeta production.

Related Experiment Videos

  • Examined Abeta production in primary cortical neurons from wild-type and transgenic mice, including those with the Swedish APP mutation.
  • Evaluated the effect of BACE1 siRNA on neurotoxicity induced by hydrogen peroxide (H2O2) oxidative stress.

    • Main Results:

    • BACE1 siRNA demonstrated specific suppression of BACE1 protein expression without affecting BACE2.
    • Reduced production of APP betaCTF and Abeta was observed in BACE1 siRNA-treated primary cortical neurons.
    • BACE1 siRNA pretreatment significantly reduced H2O2-induced neurotoxicity in neurons.
    • Subcellular distribution of APP and presenilin-1 remained unchanged in BACE1-suppressed cells.

    Conclusions:

    • BACE1 siRNA specifically targets and inhibits the beta-cleavage of APP, a critical step in Abeta generation.
    • BACE1 siRNA demonstrates potential as a therapeutic strategy for Alzheimer's disease by reducing Abeta production and neurotoxicity.