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Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin
Extracellular amyloid β-protein (1-42) (Aβ42) aggregates have been recognized as toxic agents for neural cells in vivo and in vitro. The aim of this study was to investigate the cytotoxic effects of extracellular Aβ42 aggregates in soluble (or suspended, SAβ42) and deposited (or attached, DAβ42) for...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775237/ https://www.ncbi.nlm.nih.gov/pubmed/36551236 http://dx.doi.org/10.3390/biom12121808 |
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author | Zhang, Tianyu Song, Chuli Li, He Zheng, Yanru Zhang, Yingjiu |
author_facet | Zhang, Tianyu Song, Chuli Li, He Zheng, Yanru Zhang, Yingjiu |
author_sort | Zhang, Tianyu |
collection | PubMed |
description | Extracellular amyloid β-protein (1-42) (Aβ42) aggregates have been recognized as toxic agents for neural cells in vivo and in vitro. The aim of this study was to investigate the cytotoxic effects of extracellular Aβ42 aggregates in soluble (or suspended, SAβ42) and deposited (or attached, DAβ42) forms on cell adhesion/re-adhesion, neurite outgrowth, and intracellular scaffold palladin using the neural cell lines SH-SY5Y and HT22, and to elucidate the potential relevance of these effects. The effect of extracellular Aβ42 on neural cell adhesion was directly associated with their neurotrophic or neurotoxic activity, with SAβ42 aggregates reducing cell adhesion and associated live cell de-adherence more than DAβ42 aggregates, while causing higher mortality. The reduction in cell adhesion due to extracellular Aβ42 aggregates was accompanied by the impairment of neurite outgrowth, both in length and number, and similarly, SAβ42 aggregates impaired the extension of neurites more severely than DAβ42 aggregates. Further, the disparate changes of intracellular palladin induced by SAβ42 and DAβ42 aggregates, respectively, might underlie their aforementioned effects on target cells. Further, the use of anti-oligomeric Aβ42 scFv antibodies revealed that extracellular Aβ42 aggregates, especially large DAβ42 aggregates, had some independent detrimental effects, including physical barrier effects on neural cell adhesion and neuritogenesis in addition to their neurotoxicity, which might be caused by the rigid C-terminal clusters formed between adjacent Aβ42 chains in Aβ42 aggregates. Our findings, concerning how scaffold palladin responds to extracellular Aβ42 aggregates, and is closely connected with declines in cell adhesion and neurite outgrowth, provide new insights into the cytotoxicity of extracellular Aβ42 aggregates in Alzheimer disease. |
format | Online Article Text |
id | pubmed-9775237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97752372022-12-23 Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin Zhang, Tianyu Song, Chuli Li, He Zheng, Yanru Zhang, Yingjiu Biomolecules Article Extracellular amyloid β-protein (1-42) (Aβ42) aggregates have been recognized as toxic agents for neural cells in vivo and in vitro. The aim of this study was to investigate the cytotoxic effects of extracellular Aβ42 aggregates in soluble (or suspended, SAβ42) and deposited (or attached, DAβ42) forms on cell adhesion/re-adhesion, neurite outgrowth, and intracellular scaffold palladin using the neural cell lines SH-SY5Y and HT22, and to elucidate the potential relevance of these effects. The effect of extracellular Aβ42 on neural cell adhesion was directly associated with their neurotrophic or neurotoxic activity, with SAβ42 aggregates reducing cell adhesion and associated live cell de-adherence more than DAβ42 aggregates, while causing higher mortality. The reduction in cell adhesion due to extracellular Aβ42 aggregates was accompanied by the impairment of neurite outgrowth, both in length and number, and similarly, SAβ42 aggregates impaired the extension of neurites more severely than DAβ42 aggregates. Further, the disparate changes of intracellular palladin induced by SAβ42 and DAβ42 aggregates, respectively, might underlie their aforementioned effects on target cells. Further, the use of anti-oligomeric Aβ42 scFv antibodies revealed that extracellular Aβ42 aggregates, especially large DAβ42 aggregates, had some independent detrimental effects, including physical barrier effects on neural cell adhesion and neuritogenesis in addition to their neurotoxicity, which might be caused by the rigid C-terminal clusters formed between adjacent Aβ42 chains in Aβ42 aggregates. Our findings, concerning how scaffold palladin responds to extracellular Aβ42 aggregates, and is closely connected with declines in cell adhesion and neurite outgrowth, provide new insights into the cytotoxicity of extracellular Aβ42 aggregates in Alzheimer disease. MDPI 2022-12-02 /pmc/articles/PMC9775237/ /pubmed/36551236 http://dx.doi.org/10.3390/biom12121808 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Tianyu Song, Chuli Li, He Zheng, Yanru Zhang, Yingjiu Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin |
title | Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin |
title_full | Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin |
title_fullStr | Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin |
title_full_unstemmed | Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin |
title_short | Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin |
title_sort | different extracellular β-amyloid (1-42) aggregates differentially impair neural cell adhesion and neurite outgrowth through differential induction of scaffold palladin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775237/ https://www.ncbi.nlm.nih.gov/pubmed/36551236 http://dx.doi.org/10.3390/biom12121808 |
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