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Intracellular sAPP retention in response to Aβ is mapped to cytoskeleton‐associated structures
Author(s) -
Henriques Ana Gabriela,
Vieira Sandra Isabel,
CrespoLópez Maria Elena,
Guiomar de Oliveira Márcio A.,
da Cruz e Silva Edgar F.,
da Cruz e Silva Odete A.B.
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21959
Subject(s) - intracellular , extracellular , neurodegeneration , microbiology and biotechnology , cytoskeleton , amyloid precursor protein , amyloid (mycology) , biology , chemistry , alzheimer's disease , biochemistry , cell , medicine , disease , botany
Abstract Amyloid β (Aβ) contributes to neurodegeneration in Alzheimer's disease and provides a close association between molecular events and pathology, although the underlying molecular mechanisms are unclear. In the work described here, Aβ did not induce amyloid precursor protein (APP) expression, but APP processing/trafficking was markedly affected. In COS‐7 cells, Aβ provokes retention of intracellular sAPPα (isAPPα). Intracellular holo‐APP levels remain unchanged, and extracellular total sAPP increases, although extracellular sAPPα alone was not altered significantly. In primary neuronal cultures and PC12 cells, isAPP also increased, but this was mirrored by a decrease in extracellular total sAPP. The isAPP retention was particularly associated with the cytoskeletal fraction. The retention “per se” occurred in vesicular‐like densities, negative for a C‐terminal antibody and strongly positive for the 6E10 antibody, clearly showing abnormal intracellular accumulation of sAPPα in response to Aβ. Our data support a dynamic model for intracellular retention of sAPPα as an early response to Aβ exposure. Particularly noteworthy was the observation that removal of Aβ reversed the isAPP accumulation. Mechanistically, these findings disclose an attractive physiological response, revealing the capacity of cells to deal with adverse effects induced by Aβ. © 2008 Wiley‐Liss, Inc.