Title:Microglial Cathepsin B and Porphyromonas gingivalis Gingipains as Potential Therapeutic Targets for Sporadic Alzheimer’s Disease
Volume: 19
Issue: 7
Author(s): Hiroshi Nakanishi*, Saori Nonaka and Zhou Wu
Affiliation:
- Department of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153,Japan
Keywords:
Alzheimer`s disease, cathepsin B, gingipain, microglia, neuroinflammation, periodontitis, Porphylomonas gingivalis.
Abstract: Many efforts have been made to develop therapeutic agents for Alzheimer’s Disease (AD)
based on the amyloid cascade hypothesis, but there is no effective therapeutic agent at present. Now,
much attention has been paid to infiltrate pathogens in the brain as a trigger of AD. These pathogens,
or their virulence factors, may directly cross a weakened blood-brain barrier, reach the brain and cause
neurological damage by eliciting neuroinflammation. Moreover, there is growing clinical evidence of
a correlation between periodontitis and cognitive decline in AD patients. Recent studies have revealed
that microglial cathepsin B is increasingly induced by lipopolysaccharide of Porphylomonas gingivalis,
a major pathogen of periodontal disease. Moreover, gingipains produced by P. gingivalis play
critical roles in neuroinflammation mediated by microglia and cognitive decline in mice. Furthermore,
an orally bioavailable and brain-permeable inhibitor of gingipain is now being tested in AD patients. It
is largely expected that clinical studies countering bacterial virulence factors may pave the way to establish
the prevention and early treatment of AD.
