Periodontal bacteria cleave glycogen synthase-3 kinase
What is it about?
This study provides a mechanistic link between GSK-β activation by the purified Porphyromonas gingivalis lipopolysaccharide (LPS) and an unknown factor from Actinomyces naeslundii. Both of these aforementioned bacteria are found in periodontal disease pockets that form within the gum tissue around teeth. Tau protein binds neurofibrillary tangles which is one of the two hallmark lesions in Alzheimer’s disease (AD). The neurofibrillary tangles are hyperphosphorylated. What triggers tau hyperphosphorylation is poorly understood except for knowing the enzymes that are responsible for this post-translational modification. Our gene array data from the in vitro application of P. gingivalis LPS demonstrated increased synthesis of GSK-β and its protein analysis showed that it was being cleaved as fast as it was being manufactured by the cell’s gene factory. The smaller cleaved fragment was able to enter the nucleus of the tested neurons, which in turn, switched on downstream genes including kinases responsible for tau phosphorylation and inflammatory genes. GSK-β activation is involved in AD pathology through phosphorylation of tau protein either directly or by activating other kinases that can further phosphorylate tau and microglia mediated neuroinflammation linking periodontal disease and AD.
Why is it important?
For the first time, it highlights a mechanistic link with the GSK-β activation and links with tau phosphorylation and inflammation in AD.