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Title:
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Pro-NGF from Alzheimer's disease and normal human brain displays distinctive abilities to induce processing and nuclear translocation of intracellular domain of p75NTR and apoptosis.
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Author:
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Podlesniy, Petar; Kichev, Anton Vladimirov; Pedraza, Carlos; Saurat, Jordi; Encinas Martín, Mario; Pérez, Begoña; Ferrer, Isidre; Espinet Mestre, Carme
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Notes:
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The pro form of neurotrophic growth factor (pro-NGF),
purified by chromatography from human Alzheimer’s
disease (AD)-affected brains (ADhbi-pro-NGF), has been
shown to induce apoptotic cell death in neuronal cell
cultures through its interaction with the p75 neurotrophin
receptor (p75NTR). In the present work,we report
that ADhbi-pro-NGF stimulates processing of p75NTR
with - and -secretases, yielding a 20-kd intracellular
domain (p75ICD) that translocates to the nucleus. This
process was accompanied by delayed apoptosis. In AD,
p75ICD was significantly increased in human entorhinal
cortex. Although human frontal cortex has been described
as showing a higher pro-NGF increase in AD,
the increase in the entorhinal cortex paralleled p75NTR
processing in its intracellular domain. In addition, pro-
NGF isolated from AD-affected brains differed functionally
from pro-NGF isolated from comparably aged control
brains, with pro-NGF isolated from control brains
being unstable and undergoing degradation to NGF
when added to cell culture. As p75ICD and pro-NGF are
both mediators of apoptosis and are both found in increased
levels in the cerebral cortex in AD, the present
data have implications for understanding neuronal
degeneration in AD. |
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Subject(s):
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-Alzheimer, Malaltia d'
-Sistema nerviós--Malalties |
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Rights:
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(c) American Society for Investigative Pathology, 2006
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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Document type:
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article
publishedVersion |
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Published by:
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Elsevier Inc
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Share:
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