The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation

Abstract One of the hallmarks of the most common neurodegenerative disease, Alzheimer’s disease (AD), is the extracellular deposition and aggregation of Amyloid Beta (Aβ)-peptides in the brain. Previous studies have shown that select metal ions, most specifically copper (Cu) and zinc (Zn) ions, have...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stéphane L. Benoit, Robert J. Maier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0ec3b635d684dfc8f53839f454dbc95
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d0ec3b635d684dfc8f53839f454dbc95
record_format	dspace
spelling	oai:doaj.org-article:d0ec3b635d684dfc8f53839f454dbc952021-12-02T11:45:03ZThe nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation10.1038/s41598-021-86060-12045-2322https://doaj.org/article/d0ec3b635d684dfc8f53839f454dbc952021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86060-1https://doaj.org/toc/2045-2322Abstract One of the hallmarks of the most common neurodegenerative disease, Alzheimer’s disease (AD), is the extracellular deposition and aggregation of Amyloid Beta (Aβ)-peptides in the brain. Previous studies have shown that select metal ions, most specifically copper (Cu) and zinc (Zn) ions, have a synergistic effect on the aggregation of Aβ-peptides. In the present study, inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal content of a commercial recombinant human Aβ40 peptide. Cu and Zn were among the metals detected; unexpectedly, nickel (Ni) was one of the most abundant elements. Using a fluorescence-based assay, we found that Aβ40 peptide in vitro aggregation was enhanced by addition of Zn2+ and Ni2+, and Ni2+-induced aggregation was facilitated by acidic conditions. Nickel binding to Aβ40 peptide was confirmed by isothermal titration calorimetry. Addition of the Ni-specific chelator dimethylglyoxime (DMG) inhibited Aβ40 aggregation in absence of added metal, as well as in presence of Cu2+ and Ni2+, but not in presence of Zn2+. Finally, mass spectrometry analysis revealed that DMG can coordinate Cu or Ni, but not Fe, Se or Zn. Taken together, our results indicate that Ni2+ ions enhance, whereas nickel chelation inhibits, Aβ peptide in vitro aggregation. Hence, DMG-mediated Ni-chelation constitutes a promising approach towards inhibiting or slowing down Aβ40 aggregation.Stéphane L. BenoitRobert J. MaierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stéphane L. Benoit Robert J. Maier The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
description	Abstract One of the hallmarks of the most common neurodegenerative disease, Alzheimer’s disease (AD), is the extracellular deposition and aggregation of Amyloid Beta (Aβ)-peptides in the brain. Previous studies have shown that select metal ions, most specifically copper (Cu) and zinc (Zn) ions, have a synergistic effect on the aggregation of Aβ-peptides. In the present study, inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal content of a commercial recombinant human Aβ40 peptide. Cu and Zn were among the metals detected; unexpectedly, nickel (Ni) was one of the most abundant elements. Using a fluorescence-based assay, we found that Aβ40 peptide in vitro aggregation was enhanced by addition of Zn2+ and Ni2+, and Ni2+-induced aggregation was facilitated by acidic conditions. Nickel binding to Aβ40 peptide was confirmed by isothermal titration calorimetry. Addition of the Ni-specific chelator dimethylglyoxime (DMG) inhibited Aβ40 aggregation in absence of added metal, as well as in presence of Cu2+ and Ni2+, but not in presence of Zn2+. Finally, mass spectrometry analysis revealed that DMG can coordinate Cu or Ni, but not Fe, Se or Zn. Taken together, our results indicate that Ni2+ ions enhance, whereas nickel chelation inhibits, Aβ peptide in vitro aggregation. Hence, DMG-mediated Ni-chelation constitutes a promising approach towards inhibiting or slowing down Aβ40 aggregation.
format	article
author	Stéphane L. Benoit Robert J. Maier
author_facet	Stéphane L. Benoit Robert J. Maier
author_sort	Stéphane L. Benoit
title	The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
title_short	The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
title_full	The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
title_fullStr	The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
title_full_unstemmed	The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
title_sort	nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d0ec3b635d684dfc8f53839f454dbc95
work_keys_str_mv	AT stephanelbenoit thenickelchelatordimethylglyoximeinhibitshumanamyloidbetapeptideinvitroaggregation AT robertjmaier thenickelchelatordimethylglyoximeinhibitshumanamyloidbetapeptideinvitroaggregation AT stephanelbenoit nickelchelatordimethylglyoximeinhibitshumanamyloidbetapeptideinvitroaggregation AT robertjmaier nickelchelatordimethylglyoximeinhibitshumanamyloidbetapeptideinvitroaggregation
_version_	1718395310067154944

The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation

Ejemplares similares