Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.

The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has be...

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Autores principales:	Ina Caesar, Maria Jonson, K Peter R Nilsson, Stefan Thor, Per Hammarström
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/911ddf1bf50e46d883d390f377823301
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spelling	oai:doaj.org-article:911ddf1bf50e46d883d390f3778233012021-11-18T07:28:25ZCurcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.1932-620310.1371/journal.pone.0031424https://doaj.org/article/911ddf1bf50e46d883d390f3778233012012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22348084/?tool=EBIhttps://doaj.org/toc/1932-6203The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila.Ina CaesarMaria JonsonK Peter R NilssonStefan ThorPer HammarströmPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31424 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ina Caesar Maria Jonson K Peter R Nilsson Stefan Thor Per Hammarström Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
description	The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila.
format	article
author	Ina Caesar Maria Jonson K Peter R Nilsson Stefan Thor Per Hammarström
author_facet	Ina Caesar Maria Jonson K Peter R Nilsson Stefan Thor Per Hammarström
author_sort	Ina Caesar
title	Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
title_short	Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
title_full	Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
title_fullStr	Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
title_full_unstemmed	Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
title_sort	curcumin promotes a-beta fibrillation and reduces neurotoxicity in transgenic drosophila.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/911ddf1bf50e46d883d390f377823301
work_keys_str_mv	AT inacaesar curcuminpromotesabetafibrillationandreducesneurotoxicityintransgenicdrosophila AT mariajonson curcuminpromotesabetafibrillationandreducesneurotoxicityintransgenicdrosophila AT kpeterrnilsson curcuminpromotesabetafibrillationandreducesneurotoxicityintransgenicdrosophila AT stefanthor curcuminpromotesabetafibrillationandreducesneurotoxicityintransgenicdrosophila AT perhammarstrom curcuminpromotesabetafibrillationandreducesneurotoxicityintransgenicdrosophila
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Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.

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