Science exchange logo white
  • Solutions
      Buyers

      We are making R&D services readily available to every organization that seeks to make scientific impact. Learn More

      Providers

      We are changing the way providers access and engage customers to streamline the sale and delivery of R&D services. Learn More

      Industries Agriscience Animal Health Basic Research Biopharmaceutical Chemicals Consumer Health Food Science Medical Devices
      Reproducibility

      We believe that good experiments can and should be independently replicated and validated. Learn More

  • Resources
    Innovation Blog
    Customer Stories
    Events
    Industry Trends
    News
    Product Updates
    Help Center
  • About
    About
    Our Story
    Leadership
    Partners
    Join the Team
  • Contact
  • Log In Sign Up
  • Get a Demo
  • Aβ oligomer toxicity inhibitor protects memory in models of synaptic toxicity.

    Br J Pharmacol. 167(2):383-92. doi: 10.1111/j.1476-5381.2012.01973.x. September 2012. View on PubMed.
  • Authors

    Scopes DI, O'Hare E, Jeggo R, Whyment AD, Spanswick D, Kim EM, Gannon J, Amijee H, and Treherne JM
  • Abstract

    BACKGROUND AND PURPOSEAmyloid-β (Aβ) aggregation into synaptotoxic, prefibrillar oligomers is a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The pharmacological and neuroprotective properties of a novel Aβ aggregation inhibitor, SEN1269, were investigated on aggregation and cell viability and in test systems relevant to synaptic function and memory, using both synthetic Aβ(1-42) and cell-derived Aβ oligomers.EXPERIMENTAL APPROACHSurface plasmon resonance studies measured binding of SEN1269 to Aβ(1-42) . Thioflavin-T fluorescence and MTT assays were used to measure its ability to block Aβ(1-42) -induced aggregation and reduction in cell viability. In vitro and in vivo long-term potentiation (LTP) experiments measured the effect of SEN1269 on deficits induced by synthetic Aβ(1-42) and cell-derived Aβ oligomers. Following i.c.v. administration of the latter, a complex (alternating-lever cyclic ratio) schedule of operant responding measured effects on memory in freely moving rats.KEY RESULTSSEN1269 demonstrated direct binding to monomeric Aβ(1-42) , produced a concentration-related blockade of Aβ(1-42) aggregation and protected neuronal cell lines exposed to Aβ(1-42) . In vitro, SEN1269 alleviated deficits in hippocampal LTP induced by Aβ(1-42) and cell-derived Aβ oligomers. In vivo, SEN1269 reduced the deficits in LTP and memory induced by i.c.v. administration of cell-derived Aβ oligomers.CONCLUSIONS AND IMPLICATIONSSEN1269 protected cells exposed to Aβ(1-42) , displayed central activity with respect to reducing Aβ-induced neurotoxicity and was neuroprotective in electrophysiological and behavioural models of memory relevant to Aβ-induced neurodegeneration. It represents a promising lead for designing inhibitors of Aβ-mediated synaptic toxicity as potential neuroprotective agents for treating AD.

Science exchange logo white

  • Facebook
  • Twitter
  • LinkedIn

Solutions

  • Buyers
  • Providers
  • Reproducibility

Industries

  • Agriscience
  • Animal Health
  • Basic Research
  • Biopharmaceutical
  • Chemicals
  • Consumer Health
  • Food Science
  • Medical Devices

Resources

  • Innovation Blog
  • Customer Stories
  • Events
  • Industry Trends
  • News
  • Product Updates

About

  • Our Story
  • Leadership
  • Partners
  • Join the Team

Support

  • Contact Us
  • Help Center
  • Trust
  • Terms of Use
  • Privacy Policy

Copyright © 2021 Science Exchange, Inc. All rights reserved.