Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 2, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2010.12.010
Keywords
HSV-1; Autophagy; beta-amyloid; APP; Amyloidogenic pathway; Lysosome; Alzheimer's disease
Categories
Funding
- Ministerio de Educacion y Ciencia [GEN2003-20235-C05-05]
- Obra Social Caja Madrid
- Comunidad Autonoma de Madrid [GR/SAL/0783/2004]
- Ministerio de Sanidad y Consumo (Instituto de Salud Carlos III)
- Asociacion de Familiares de Enfermos de Alzheimer (AFAL)
- Fundacion Ramon Areces
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Mounting evidence suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of Alzheimer's disease (AD). Epidemiological analyses have shown that HSV-1 is a risk factor for AD in people with at least 1 type 4 allele of the apolipoprotein E gene. Recent studies have also suggested that HSV-1 contributes to the appearance of the biochemical anomalies characteristic of AD brains. In addition, autophagic activity appears to be reduced with aging, and the final stages of autophagy in neurodegenerative process appear to be impaired. The present work reports that HSV-1 provokes the strong intracellular accumulation of both the main species of beta-amyloid (A beta) in the autophagic compartments and that it is associated with a marked inhibition of A beta secretion. Autophagosomes containing A beta failed to fuse with lysosomes in HSV-1-infected cells, indicating the impaired degradation of A beta localized in the autophagic vesicles. In addition, HSV-1 infection was associated with the inhibition of the nonamyloidogenic pathway of amyloid precursor protein (APP) processing without significantly affecting the activity of the secretases involved in the amyloidogenic pathway. Taken together, these data suggest that HSV-1 infection modulates autophagy and amyloid precursor protein processing, contributing to the accumulation of A beta characteristic of AD. (C) 2012 Elsevier Inc. All rights reserved.
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