Title

The excitotoxin quinolinic acid induces tau phosphorylation in human neurons.

Journal

PloS one

Volume

4

Issue

None

Pages

e6344

Date

2009-07-22

Authors

Braidy N | Brew BJ | Cullen KM | Guillemin GJ | Rahman A | Ting K

Kynurenic pathway is overactive in AD. QA is co-localized with hyperphosphorylated tau within cortical neurons in AD brain. In primary cultures of human neurons, QA treatment increased tau phosphorylation at serine 199/202, threonine 231 and serine 396/404 in a dose dependent manner. This increase in tau phosphorylation was paralleled by a substantial decrease in the total protein phosphatase activity, mostly in PP2A expression and modest in PP1.

Using PCR arrays, QA significantly induces 10 genes in human neurons known to be associated with AD pathology with 6 belonging to pathways involved in tau phosphorylation and 4 of them in neuroprotection.

QA appears to act through NMDA receptor activation similar to other agonists, glutamate and NMDA and was abrogated by the NMDAR antagonist memantine. NMDA receptor agonists, glutamate and NMDA at equimolar concentrations (500 nM) increased tau phosphorylation at serine 199/202 (AT8) and threonine 231 (AT-180), similar to QA.

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