Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ

Abstract Amyloid β (Aβ) peptide aggregation plays a central role in Alzheimer’s disease (AD) etiology. AD drug candidates have included small molecules or peptides directed towards inhibition of Aβ fibrillogenesis. Although some Aβ-derived peptide fragments suppress Aβ fibril growth, comprehensive a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Faisal Abedin, Nabin Kandel, Suren A. Tatulian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2af0e39adc3a49bca758d8f9304b214d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2af0e39adc3a49bca758d8f9304b214d
record_format	dspace
spelling	oai:doaj.org-article:2af0e39adc3a49bca758d8f9304b214d2021-12-02T19:16:46ZEffects of Aβ-derived peptide fragments on fibrillogenesis of Aβ10.1038/s41598-021-98644-y2045-2322https://doaj.org/article/2af0e39adc3a49bca758d8f9304b214d2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98644-yhttps://doaj.org/toc/2045-2322Abstract Amyloid β (Aβ) peptide aggregation plays a central role in Alzheimer’s disease (AD) etiology. AD drug candidates have included small molecules or peptides directed towards inhibition of Aβ fibrillogenesis. Although some Aβ-derived peptide fragments suppress Aβ fibril growth, comprehensive analysis of inhibitory potencies of peptide fragments along the whole Aβ sequence has not been reported. The aim of this work is (a) to identify the region(s) of Aβ with highest propensities for aggregation and (b) to use those fragments to inhibit Aβ fibrillogenesis. Structural and aggregation properties of the parent Aβ1–42 peptide and seven overlapping peptide fragments have been studied, i.e. Aβ1–10 (P1), Aβ6–15 (P2), Aβ11–20 (P3), Aβ16–25 (P4), Aβ21–30 (P5), Aβ26–36 (P6), and Aβ31–42 (P7). Structural transitions of the peptides in aqueous buffer have been monitored by circular dichroism and Fourier transform infrared spectroscopy. Aggregation and fibrillogenesis were analyzed by light scattering and thioflavin-T fluorescence. The mode of peptide-peptide interactions was characterized by fluorescence resonance energy transfer. Three peptide fragments, P3, P6, and P7, exhibited exceptionally high propensity for β-sheet formation and aggregation. Remarkably, only P3 and P6 exerted strong inhibitory effect on the aggregation of Aβ1–42, whereas P7 and P2 displayed moderate inhibitory potency. It is proposed that P3 and P6 intercalate between Aβ1–42 molecules and thereby inhibit Aβ1–42 aggregation. These findings may facilitate therapeutic strategies of inhibition of Aβ fibrillogenesis by Aβ-derived peptides.Faisal AbedinNabin KandelSuren A. TatulianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Faisal Abedin Nabin Kandel Suren A. Tatulian Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
description	Abstract Amyloid β (Aβ) peptide aggregation plays a central role in Alzheimer’s disease (AD) etiology. AD drug candidates have included small molecules or peptides directed towards inhibition of Aβ fibrillogenesis. Although some Aβ-derived peptide fragments suppress Aβ fibril growth, comprehensive analysis of inhibitory potencies of peptide fragments along the whole Aβ sequence has not been reported. The aim of this work is (a) to identify the region(s) of Aβ with highest propensities for aggregation and (b) to use those fragments to inhibit Aβ fibrillogenesis. Structural and aggregation properties of the parent Aβ1–42 peptide and seven overlapping peptide fragments have been studied, i.e. Aβ1–10 (P1), Aβ6–15 (P2), Aβ11–20 (P3), Aβ16–25 (P4), Aβ21–30 (P5), Aβ26–36 (P6), and Aβ31–42 (P7). Structural transitions of the peptides in aqueous buffer have been monitored by circular dichroism and Fourier transform infrared spectroscopy. Aggregation and fibrillogenesis were analyzed by light scattering and thioflavin-T fluorescence. The mode of peptide-peptide interactions was characterized by fluorescence resonance energy transfer. Three peptide fragments, P3, P6, and P7, exhibited exceptionally high propensity for β-sheet formation and aggregation. Remarkably, only P3 and P6 exerted strong inhibitory effect on the aggregation of Aβ1–42, whereas P7 and P2 displayed moderate inhibitory potency. It is proposed that P3 and P6 intercalate between Aβ1–42 molecules and thereby inhibit Aβ1–42 aggregation. These findings may facilitate therapeutic strategies of inhibition of Aβ fibrillogenesis by Aβ-derived peptides.
format	article
author	Faisal Abedin Nabin Kandel Suren A. Tatulian
author_facet	Faisal Abedin Nabin Kandel Suren A. Tatulian
author_sort	Faisal Abedin
title	Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
title_short	Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
title_full	Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
title_fullStr	Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
title_full_unstemmed	Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
title_sort	effects of aβ-derived peptide fragments on fibrillogenesis of aβ
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2af0e39adc3a49bca758d8f9304b214d
work_keys_str_mv	AT faisalabedin effectsofabderivedpeptidefragmentsonfibrillogenesisofab AT nabinkandel effectsofabderivedpeptidefragmentsonfibrillogenesisofab AT surenatatulian effectsofabderivedpeptidefragmentsonfibrillogenesisofab
_version_	1718376903810744320

Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ

Ejemplares similares