Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
Stephen S Dominy, Casey Lynch, Florian Ermini, Malgorzata Benedyk, Agata Marczyk, Andrei Konradi, Mai Nguyen, Ursula Haditsch, Debasish Raha, Christina Griffin, Leslie J Holsinger, Shirin Arastu-Kapur, Samer Kaba, Alexander Lee, Mark I Ryder, Barbara Potempa, Piotr Mydel, Annelie Hellvard, Karina Adamowicz, Hatice Hasturk Show all
SCIENCE ADVANCES | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019
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 inhi..View full abstract
Awarded by National Science Center, Poland
Awarded by NIH/NIDCR
Awarded by NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
P.M. was supported by National Science Center 2016/23/B/NZ5/011469, Poland. J.P. was supported by NIH/NIDCR grant R01DE022597. This work was funded by Cortexyme Inc.