Herpes simplex virus (HSV) types 1 and 2 are neurotropic viruses that
establish lifelong latent infections in neurons. Mounting evidence
suggests that HSV-1 infection is involved in the pathogenesis of
Alzheimer’s disease (AD). The relationships between other herpesvirus
infections and events associated with neurodegeneration have not,
however, been extensively studied. The present work reports that HSV-2
infection leads to the strong accumulation of hyperphosphorylated tau
and the amyloid-β peptides Aβ40 and Aβ42 (all major pathological
hallmarks of AD) in human SK-N-MC neuroblastoma cells. Infection is also
associated with a marked reduction in the amount of Aβ40 secreted, and
in the proteolytic fragments of the amyloid-β precursor protein (APP)
(secreted APPα and the α-C-terminal fragment). These results indicate
that HSV-2 infection inhibits the non-amyloidogenic pathway of APP
processing and impairs Aβ secretion in these cells. In addition, HSV-2
induces the accumulation of intracellular autophagic compartments
containing Aβ due to a failure in the late stages of autophagy. To our
knowledge, this is the first report to show that HSV-2 infection
strongly alters the tau phosphorylation state, APP processing, and
autophagic process in human neuroblastoma cells, leading to the
appearance of AD-like neurodegeneration markers.
establish lifelong latent infections in neurons. Mounting evidence
suggests that HSV-1 infection is involved in the pathogenesis of
Alzheimer’s disease (AD). The relationships between other herpesvirus
infections and events associated with neurodegeneration have not,
however, been extensively studied. The present work reports that HSV-2
infection leads to the strong accumulation of hyperphosphorylated tau
and the amyloid-β peptides Aβ40 and Aβ42 (all major pathological
hallmarks of AD) in human SK-N-MC neuroblastoma cells. Infection is also
associated with a marked reduction in the amount of Aβ40 secreted, and
in the proteolytic fragments of the amyloid-β precursor protein (APP)
(secreted APPα and the α-C-terminal fragment). These results indicate
that HSV-2 infection inhibits the non-amyloidogenic pathway of APP
processing and impairs Aβ secretion in these cells. In addition, HSV-2
induces the accumulation of intracellular autophagic compartments
containing Aβ due to a failure in the late stages of autophagy. To our
knowledge, this is the first report to show that HSV-2 infection
strongly alters the tau phosphorylation state, APP processing, and
autophagic process in human neuroblastoma cells, leading to the
appearance of AD-like neurodegeneration markers.
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