Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation.

Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Research Abstract Details 

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Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Abstract Text:

Matthew A Wozniak,Ruth F Itzhaki,Suzanne J Shipley,Curtis B Dobson,Matthew A Wozniak,Ruth F Itzhaki,Suzanne J Shipley,Curtis B Dobson,

It is uncertain whether environmental factors contribute to the formation of senile plaques and neurofibrillary tangles, the abnormal features that define the Alzheimer's disease (AD) brain. We previously proposed that herpes simplex virus type 1 (HSV1) is a strong risk factor for AD when it is present in the brains of people who possess the type 4 allele of the apolipoprotein E gene (APOE-epsilon4); however a direct biochemical link between viral infection and the development of the AD pathological features has never previously been examined. Here we show that infection of cultured neuronal and glial cells with HSV1 leads to a dramatic increase in the intracellular levels of beta-amyloid (Abeta) 1-40 and 1-42, whilst levels of amyloid precursor protein (APP) in cells decrease. Similarly, Abeta1-42 deposits are present in mouse brain after HSV1 infection. In the cultured cells the mechanism involves increased Abeta production, rather than merely greater retention of cellular Abeta, as levels of beta-site APP-cleaving enzyme (BACE-1) and of nicastrin, a component of gamma-secretase, both increase in HSV1-infected cells. These novel data show that HSV1 can directly contribute to the development of senile plaques.

Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Publishing Authors By Initials

MA Wozniak,RF Itzhaki,SJ Shipley,CB Dobson,MA Wozniak,RF Itzhaki,SJ Shipley,CB Dobson,

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Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuroscience letters

VOLUME: 429

Page Numbers: 95-100

Journal Abbreviation: Neurosci. Lett.

ISSN: 0304-3940

DAY: 13

MONTH: 10

YEAR: 2007

Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation.

AFFILIATION: Faculty of Life Sciences, The University of Manchester, PO Box 88, Sackville Street, Manchester M60 1QD, UK.

Country: Ireland

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MEDLINETA: Neurosci Lett

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