Questions, Feedback & Help
Send us an email and we'll get back to you ASAP. Or you can read our Frequently Asked Questions.
  • page settings
  • hide sidebar
  • show empty fields
  • layout
  • (too narrow)
  • open all
  • close all
Resources » Paper

ayyadevara, srinivas et al. (2019) International Worm Meeting "A novel microtubule-binding drug attenuates and reverses protein aggregation in animal models of Alzheimer's disease."

  • History

  • Referenced

  • Tree Display

  • My Favorites

  • My Library

  • Comments on ayyadevara, srinivas et al. (2019) International Worm Meeting "A novel microtubule-binding drug attenuates and reverses protein aggregation in animal models of Alzheimer's disease." (0)

  • Overview

    Status:
    Publication type:
    Meeting_abstract
    WormBase ID:
    WBPaper00058498

    Ayyadevara, Srinivas, Kakraba, Samuel, Penthala, Narsimha Reddy, Balasubramaniam, Meenakshisundaram, Ganne, Akshatha, Liu , Ling, Alla, Ramani, Bommagani, Shoban Babu, Barger, Steven, Griffin, Sue, Crooks, Peter, & Shmookler Reis, Robert (2019). A novel microtubule-binding drug attenuates and reverses protein aggregation in animal models of Alzheimer's disease presented in International Worm Meeting. Unpublished information; cite only with author permission.

    Age-progressive neurodegenerative pathologies, including Alzheimer's disease, are distinguished and diagnosed by disease-specific components of intra- or extra-cellular aggregates. Increasing evidence suggests that neuroinflammation promotes protein aggregation, and is involved in the etiology of neurological diseases. We synthesized and tested analogues of the naturally occurring tubulin-binding compound, combretastatin A-4. One such analogue, PNR502, markedly reduced the quantity of Alzheimer-associated amyloid aggregates in the BRI-A?1-42 mouse model of Alzheimer's disease, while blunting the ability of the pro-inflammatory cytokine IL-1? to raise levels of amyloid plaque and its protein precursors in a neuronal cell-culture model. In transgenic C. elegans strains that express human A?1-42 in muscle or neurons, PNR502 rescued A?-induced disruption of motility (3.8-fold, p<0.0001) or chemotaxis (1.8-fold, p<0.05), respectively. Moreover, in C. elegans with neuronal expression of A?1-42, a single day of PNR502 exposure reverses the chemotaxis deficit by 54% (p<0.01), actually exceeding the protection from longer exposure. Moreover, continuous PNR502 treatment also extends nematode lifespan 23% (p?0.001). Given that PNR502 can slow, prevent, or reverse Alzheimer-like protein aggregation in human-cell-culture and animal models, and that its principal predicted and observed binding targets are proteins previously implicated in Alzheimer's, we propose that PNR502 has therapeutic potential to inhibit cerebral A?1-42 aggregation and prevent or reverse neurodegeneration.

    Authors: Ayyadevara, Srinivas, Kakraba, Samuel, Penthala, Narsimha Reddy, Balasubramaniam, Meenakshisundaram, Ganne, Akshatha, Liu , Ling, Alla, Ramani, Bommagani, Shoban Babu, Barger, Steven, Griffin, Sue, Crooks, Peter, Shmookler Reis, Robert

    Affiliations:
    - Central Arkansas Veterans Healthcare Service, Little Rock AR 72205
    - Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205
    - BioInformatics Program, University of Arkansas for Medical Sciences and University of Arkansas at Little Rock, Little Rock, AR 72205
    - Dept Geriatrics, Univ Arkansas Med Sci, Little Rock, AR


    Tip: Seeing your name marked red? Please help us identify you.