β-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system
Almeida, Claudia G. ; Takahashi, Reisuke H. and Gouras, Gunnar K. LU
(2006)
In The Journal of Neuroscience
26(16).
p.4277-4288
- Abstract
Increasing evidence links intraneuronal β-amyloid (Aβ 42) accumulation with the pathogenesis of Alzheimer's disease (AD). In Aβ precursor protein (APP) mutant transgenic mice and in human AD brain, progressive intraneuronal accumulation of Aβ42 occurs especially in multivesicular bodies (MVBs). We hypothesized that this impairs the MVB sorting pathway. We used the trafficking of the epidermal growth factor receptor (EGFR) and TrkB receptor to investigate the MVB sorting pathway in cultured neurons. We report that, during EGF stimulation, APP mutant neurons demonstrated impaired inactivation, degradation, and ubiquitination of EGFR. EGFR degradation is dependent on translocation from MVB outer to inner membranes,... (More)
Increasing evidence links intraneuronal β-amyloid (Aβ 42) accumulation with the pathogenesis of Alzheimer's disease (AD). In Aβ precursor protein (APP) mutant transgenic mice and in human AD brain, progressive intraneuronal accumulation of Aβ42 occurs especially in multivesicular bodies (MVBs). We hypothesized that this impairs the MVB sorting pathway. We used the trafficking of the epidermal growth factor receptor (EGFR) and TrkB receptor to investigate the MVB sorting pathway in cultured neurons. We report that, during EGF stimulation, APP mutant neurons demonstrated impaired inactivation, degradation, and ubiquitination of EGFR. EGFR degradation is dependent on translocation from MVB outer to inner membranes, which is regulated by the ubiquitin-proteasome system (UPS). We provide evidence that Aβ accumulation in APP mutant neurons inhibits the activities of the proteasome and deubiquitinating enzymes. These data suggest a mechanism whereby Aβ accumulation in neurons impairs the MVB sorting pathway via the UPS in AD.
(Less)
- author
- Almeida, Claudia G.
; Takahashi, Reisuke H.
and Gouras, Gunnar K.
LU
- publishing date
- 2006-09-07
- type
- Contribution to journal
- publication status
- published
- keywords
- Alzheimer's disease, EGFR, Endocytosis, Endosome, Neuron, TrkB
- in
- The Journal of Neuroscience
- volume
- 26
- issue
- 16
- pages
- 4277 - 4288
- publisher
- Society for Neuroscience
- external identifiers
-
- scopus:33646461282
- pmid:16624948
- ISSN
- 0270-6474
- DOI
- 10.1523/JNEUROSCI.5078-05.2006
- language
- English
- LU publication?
- no
- id
- 8a43d311-956f-4cd9-84e1-785eaf4ed26c
- date added to LUP
- 2020-02-20 14:21:40
- date last changed
- 2024-06-13 12:59:55
@article{8a43d311-956f-4cd9-84e1-785eaf4ed26c,
abstract = {{<p>Increasing evidence links intraneuronal β-amyloid (Aβ <sub>42</sub>) accumulation with the pathogenesis of Alzheimer's disease (AD). In Aβ precursor protein (APP) mutant transgenic mice and in human AD brain, progressive intraneuronal accumulation of Aβ<sub>42</sub> occurs especially in multivesicular bodies (MVBs). We hypothesized that this impairs the MVB sorting pathway. We used the trafficking of the epidermal growth factor receptor (EGFR) and TrkB receptor to investigate the MVB sorting pathway in cultured neurons. We report that, during EGF stimulation, APP mutant neurons demonstrated impaired inactivation, degradation, and ubiquitination of EGFR. EGFR degradation is dependent on translocation from MVB outer to inner membranes, which is regulated by the ubiquitin-proteasome system (UPS). We provide evidence that Aβ accumulation in APP mutant neurons inhibits the activities of the proteasome and deubiquitinating enzymes. These data suggest a mechanism whereby Aβ accumulation in neurons impairs the MVB sorting pathway via the UPS in AD.</p>}},
author = {{Almeida, Claudia G. and Takahashi, Reisuke H. and Gouras, Gunnar K.}},
issn = {{0270-6474}},
keywords = {{Alzheimer's disease; EGFR; Endocytosis; Endosome; Neuron; TrkB}},
language = {{eng}},
month = {{09}},
number = {{16}},
pages = {{4277--4288}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience}},
title = {{β-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.5078-05.2006}},
doi = {{10.1523/JNEUROSCI.5078-05.2006}},
volume = {{26}},
year = {{2006}},
}