Affiliations: Faculty of Life Sciences, The University of Manchester, Manchester, UK
Correspondence:
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Corresponding author: Prof. Ruth Itzhaki, Faculty of Life Sciences (North Campus), The University of Manchester, Moffat Building, PO Box 88, Sackville Street, Manchester, M60 1QD, UK. Tel.: +44 161 306 3879; Fax: +44 161 306 4433; E-mail: ruth.itzhaki@manchester.ac.uk.
Abstract: Neurofibrillary tangles are one of the main neuropathological features of Alzheimer's disease (AD) and are composed of abnormally phosphorylated forms of a microtubule-associated protein called tau. What causes this abnormal phosphorylation is unknown. Our previous studies have implicated herpes simplex virus type 1 (HSV1) as an etiological agent in AD, and so we investigated whether infection with this virus induces AD-like tau phosphorylation. Here we demonstrate that HSV1 causes tau phosphorylation at several sites, including serine 202, threonine 212, serine 214, serine 396 and serine 404. In addition, we have elucidated the mechanism involved by showing that the virus induces glycogen synthase kinase 3β and protein kinase A, the enzymes that cause phosphorylation at these sites. Our data clearly reveal the importance of HSV1 in AD-type tau phosphorylation, and support the case that the virus is a cause of the disease. Together with our previous data, our results point to the use of antiviral agents to slow the progression of the disease.
Keywords: Alzheimer's disease, glycogen synthase kinase 3β, herpes simplex virus type 1, phosphorylation, protein kinase A, tau
