University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Dental School
  • Melbourne Dental School - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Dental School
  • Melbourne Dental School - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors

    Thumbnail
    Download
    Published version (2.360Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    266
    242
    Author
    Dominy, SS; Lynch, C; Ermini, F; Benedyk, M; Marczyk, A; Konradi, A; Nguyen, M; Haditsch, U; Raha, D; Griffin, C; ...
    Date
    2019-01-01
    Source Title
    Science Advances
    Publisher
    AMER ASSOC ADVANCEMENT SCIENCE
    University of Melbourne Author/s
    Walker, Glenn; Reynolds, Eric
    Affiliation
    Melbourne Dental School
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Dominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., Holsinger, L. J., Arastu-Kapur, S., Kaba, S., Lee, A., Ryder, M. I., Potempa, B., Mydel, P., Hellvard, A., Adamowicz, K. ,... Potempa, J. (2019). Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. SCIENCE ADVANCES, 5 (1), https://doi.org/10.1126/sciadv.aau3333.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253765
    DOI
    10.1126/sciadv.aau3333
    Abstract
    Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer's disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer's patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1-42, a component of amyloid plaques. Further, gingipains were neurotoxic in vivo and in vitro, exerting detrimental effects on tau, a protein needed for normal neuronal function. To block this neurotoxicity, we designed and synthesized small-molecule inhibitors targeting gingipains. Gingipain inhibition reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus. These data suggest that gingipain inhibitors could be valuable for treating P. gingivalis brain colonization and neurodegeneration in Alzheimer's disease.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Melbourne Dental School - Research Publications [249]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors