Clustering hinders APP α-secretase processing in the plasma membrane.
Overview
Abstract
Alzheimer’s disease is associated with the extracellular accumulation of neurotoxic Aβ-peptides in the brain. Aβ-peptides are produced via an amyloid precursor protein (APP) cleavage pathway that is initiated by the β-secretase. The majority of APP circumvents the amyloidogenic pathway due to α-secretase cleavage at the plasma membrane. In this study, we set out to identify potential mechanisms limiting α-cleavage. We employed isolated cell membranes to study α-secretase cleavage in the absence of APP delivery to the plasma membrane and internalization. We distinguish a readily cleavable and a cleavage-resistant APP pool. The cleavage-resistant and most likely immobile APP pool is organized in clusters and by this could escape the amyloidogenic pathway. In sum, our results identify that α-secretase cleavage at the plasma membrane occurs rapidly though in an incomplete manner due to the presence of cleavage-resistant APP clusters.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 2, 28 September 2026
- Authors: added Thorsten Lang (0000-0002-9128-0137); removed Thorsten Lang
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 2 authors, 5 MeSH terms, 4 funders, 73 references.
Cite
This paper
Pinkwart, K., & Lang, T. (2026). Clustering hinders APP α-secretase processing in the plasma membrane. Biophysical journal, 125(9), 2195-2212. https://
BibTeX
@article{pinkwart2026clu
author = {Pinkwart, Kerstin and Lang, Thorsten},
title = {{Clustering hinders APP α-secretase processing in the plasma membrane}},
journal = {Biophysical journal},
year = {2026},
month = apr,
volume = {125},
number = {9},
pages = {2195--2212},
publisher = {The Biophysical Society},
issn = {0006-3495},
doi = {10.1016/
url = {https://
pmid = {41933902},
pmcid = {PMC13351588}
}
RIS
TY - JOUR
AU - Pinkwart, Kerstin
AU - Lang, Thorsten
TI - Clustering hinders APP α-secretase processing in the plasma membrane
T2 - Biophysical journal
J2 - Biophys J
PY - 2026
DA - 2026/
VL - 125
IS - 9
SP - 2195
EP - 2212
SN - 0006-3495
PB - The Biophysical Society
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1016/
"type": "article-journal",
"title": "Clustering hinders APP α-secretase processing in the plasma membrane",
"container-title": "Biophysical journal",
"author": [
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"family": "Pinkwart",
"given": "Kerstin"
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"given": "Thorsten"
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"volume": "125",
"issue": "9",
"page": "2195-2212",
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"PMCID": "PMC13351588",
"ISSN": "0006-3495",
"publisher": "The Biophysical Society",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
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}
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