Abstract

Aggregated fibrils of amyloid beta (Aβ) peptide induce the neurotoxicity characteristic of Alzheimer's Disease. The inhibition of Aβ aggregation could therefore represent a therapeutic target for Alzheimer's Disease. Protein disulfide isomerase (PDI) is an oxidoreductase and chaperone that has been shown to effectively inhibit the formation of Aβ fibrils when present at the onset of aggregation. However, the potential disruption of ongoing Aβ fibrillization by PDI has not been demonstrated. We examined the disruptive effect of PDI on Aβ aggregation using a Thioflavin‐T fluorescence assay to monitor Aβ fibrillization. PDI prevented the aggregation of monomeric Aβ at a sub‐stoichiometric 1:10 molar ratio of PDI:Aβ. Fibrillization was partially inhibited by a 1:50 molar ratio of PDI:Aβ and was not affected by a 1:100 molar ratio of PDI:Aβ. As such, a 1:10 molar ratio of PDI:Aβ was used for all subsequent experiments. We next found that PDI could also disrupt Aβ fibrillization when added 2, 4, or 10 h after the initiation of aggregation. Cell culture studies using an MTS cell viability assay further demonstrated that PDI can protect neuronal cells from extracellular aggregates of Aβ when added 2 h after the initiation of aggregation. These findings demonstrate PDI is able to disrupt Aβ aggregation at sub‐stoichiometric molar ratios and support the potential use of PDI as a novel therapy for Alzheimer's Disease.Support or Funding InformationFlorida Department of Health, Ed and Ethel Moore Alzheimer's Disease Research Program Grant 8AZ12This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.