Gingipains {60000087}

Shared Reference Notes

• [1.1] 
  - 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.
• [1.2] [#Alzheimer’s disease] [#Porphyromonas gingivalis] 
  - tau to be a target of gingipain proteolysis and suggested that tau pathology in AD brains may be caused by transneural spread of P. gingivalis, tau damage by gingipain proteolysis, and activation of human proteases. They also hypothesized that gingipains might be a driver of a compensatory increase in tau production of AD patients.
• [1.3] [#Alzheimer’s disease] [#Porphyromonas gingivalis] [#Amyloid-beta] 
  - AβPP is an infection responsive protein cleaved via the amyloidogenic pathway on exposure to conditioned medium and in the presence of pro-inflammatory mediators.
• [1.4] [#Alzheimer’s disease] [#Porphyromonas gingivalis] 
  - nerve cells in the brain contain a type of protein called tau. When tau meets the gingipains enzyme, the tau released from the nerve cell. Once freed, tau physically changes, in the form of coils and non-coiling filaments. These filaments of tau then re-attach to the nerve cell and become incorporated into the lesion known as neurofibrillary tangles. - once a nerve cell dies and the free tau protein leaks into the brain, the tau may attach itself to healthy neighboring nerve cells, repeating the process and leading to further damage to the brain as the disease spreads
• [1.5] 
  - #Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. - Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate #Citrullinated Proteins. - Citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. - both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as #Rheumatoid Arthritis, #Atherosclerosis, and #Alzheimer’s disease.
• [1.6] [#Alzheimer’s disease, #Parkinson’s Disease] 
  - #Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies.

References Notes