Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation

Abstract Neuronal dysfunction and loss associated with the accumulation of amyloid-β (Aβ) in the form of extracellular amyloid plaques and hyperphosphorylated tau in the form of intraneuronal neurofibrillary tangles represent key features of Alzheimer’s disease (AD). Amyloid plaques found in the bra...

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Autores principales:	O. G. Zatsepina, O. I. Kechko, V. A. Mitkevich, S. A. Kozin, M. M. Yurinskaya, M. G. Vinokurov, M. V. Serebryakova, A. P. Rezvykh, M. B. Evgen’ev, A. A. Makarov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b138290a4e24bf4ba1259ca92fb1ffa
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spelling	oai:doaj.org-article:9b138290a4e24bf4ba1259ca92fb1ffa2021-12-02T15:09:04ZAmyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation10.1038/s41598-018-21815-x2045-2322https://doaj.org/article/9b138290a4e24bf4ba1259ca92fb1ffa2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21815-xhttps://doaj.org/toc/2045-2322Abstract Neuronal dysfunction and loss associated with the accumulation of amyloid-β (Aβ) in the form of extracellular amyloid plaques and hyperphosphorylated tau in the form of intraneuronal neurofibrillary tangles represent key features of Alzheimer’s disease (AD). Amyloid plaques found in the brains of AD patients are predominantly composed of Aβ42 and its multiple chemically or structurally modified isoforms. Recently, we demonstrated that Aβ42 with isomerised Asp7 (isoAβ42) which is one of the most abundant Aβ isoform in plaques, exhibited high neurotoxicity in human neuronal cells. Here, we show that, in SH-SY5Y neuroblastoma cells, the administration of synthetic isoAβ42 rather than intact Aβ42 resulted in a significantly higher level of protein phosphorylation, especially the phosphorylation of tau, tubulins, and matrin 3. IsoAβ42 induced a drastic reduction of tau protein levels. Our data demonstrate, for the first time, that isoAβ42, being to date the only known synthetic Aβ species to cause AD-like amyloidogenesis in an animal AD model, induced cell death by disabling structural proteins in a manner characteristic of that observed in the neurons of AD patients. The data emphasize an important role of isoAβ42 in AD progression and provide possible neurotoxicity paths for this particular isoform.O. G. ZatsepinaO. I. KechkoV. A. MitkevichS. A. KozinM. M. YurinskayaM. G. VinokurovM. V. SerebryakovaA. P. RezvykhM. B. Evgen’evA. A. MakarovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q O. G. Zatsepina O. I. Kechko V. A. Mitkevich S. A. Kozin M. M. Yurinskaya M. G. Vinokurov M. V. Serebryakova A. P. Rezvykh M. B. Evgen’ev A. A. Makarov Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation
description	Abstract Neuronal dysfunction and loss associated with the accumulation of amyloid-β (Aβ) in the form of extracellular amyloid plaques and hyperphosphorylated tau in the form of intraneuronal neurofibrillary tangles represent key features of Alzheimer’s disease (AD). Amyloid plaques found in the brains of AD patients are predominantly composed of Aβ42 and its multiple chemically or structurally modified isoforms. Recently, we demonstrated that Aβ42 with isomerised Asp7 (isoAβ42) which is one of the most abundant Aβ isoform in plaques, exhibited high neurotoxicity in human neuronal cells. Here, we show that, in SH-SY5Y neuroblastoma cells, the administration of synthetic isoAβ42 rather than intact Aβ42 resulted in a significantly higher level of protein phosphorylation, especially the phosphorylation of tau, tubulins, and matrin 3. IsoAβ42 induced a drastic reduction of tau protein levels. Our data demonstrate, for the first time, that isoAβ42, being to date the only known synthetic Aβ species to cause AD-like amyloidogenesis in an animal AD model, induced cell death by disabling structural proteins in a manner characteristic of that observed in the neurons of AD patients. The data emphasize an important role of isoAβ42 in AD progression and provide possible neurotoxicity paths for this particular isoform.
format	article
author	O. G. Zatsepina O. I. Kechko V. A. Mitkevich S. A. Kozin M. M. Yurinskaya M. G. Vinokurov M. V. Serebryakova A. P. Rezvykh M. B. Evgen’ev A. A. Makarov
author_facet	O. G. Zatsepina O. I. Kechko V. A. Mitkevich S. A. Kozin M. M. Yurinskaya M. G. Vinokurov M. V. Serebryakova A. P. Rezvykh M. B. Evgen’ev A. A. Makarov
author_sort	O. G. Zatsepina
title	Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation
title_short	Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation
title_full	Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation
title_fullStr	Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation
title_full_unstemmed	Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation
title_sort	amyloid-β with isomerized asp7 cytotoxicity is coupled to protein phosphorylation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9b138290a4e24bf4ba1259ca92fb1ffa
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Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation

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