CE can identify small molecules that selectively target soluble oligomers of amyloid β protein and display antifibrillogenic activity

Raffaella Colombo, Angelo Carotti, Marco Catto, Marco Racchi, Cristina Lanni, Laura Verga, Gabriele Caccialanza, Ersilia De Lorenzi

Research output: Contribution to journalArticle

Abstract

Soluble and toxic oligomers of amyloid β (Aβ) protein have been identified as the true neurotoxic species involved in Alzheimer's disease and considering them as targets to inhibit Aβ aggregation might have a therapeutic value. We previously set up a CE method that enables the separation and quantification of transient oligomers of Aβ protein-containing 42 amino acids (Aβ1-42) along the pathway leading to fibrils and we now demonstrate how this method can be successfully applied to examine the in vitro inhibitory effects of small molecules on Aβ oligomerization. To this end, we investigated mitoxantrone and pixantrone, two well-known anticancer drugs, as well as suramin and a suramin-like compound. By using CE, it is here shown how mitoxantrone and pixantrone either reduce or block Aβ1-42 oligomerization, while Thioflavin T spectrofluorimetric assay and transmission electron microscopy demonstrate how these two compounds also display antifibrillogenic activity. Interestingly, in vitro cell viability experiments indicated that pixantrone significantly reduces Aβ1-42 neurotoxicity.

Original languageEnglish
Pages (from-to)1418-1429
Number of pages12
JournalElectrophoresis
Volume30
Issue number8
DOIs
Publication statusPublished - 2009

Fingerprint

Amyloidogenic Proteins
Oligomers
Suramin
Mitoxantrone
Oligomerization
Molecules
Serum Amyloid A Protein
Poisons
Transmission Electron Microscopy
Assays
Cell Survival
Alzheimer Disease
Agglomeration
Cells
Transmission electron microscopy
Amino Acids
Pharmaceutical Preparations
pixantrone
Proteins
Experiments

Keywords

  • Alzheimer's disease
  • Amyloid β
  • CE
  • Mitoxantrone
  • Pixantrone

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

CE can identify small molecules that selectively target soluble oligomers of amyloid β protein and display antifibrillogenic activity. / Colombo, Raffaella; Carotti, Angelo; Catto, Marco; Racchi, Marco; Lanni, Cristina; Verga, Laura; Caccialanza, Gabriele; De Lorenzi, Ersilia.

In: Electrophoresis, Vol. 30, No. 8, 2009, p. 1418-1429.

Research output: Contribution to journalArticle

Colombo, Raffaella ; Carotti, Angelo ; Catto, Marco ; Racchi, Marco ; Lanni, Cristina ; Verga, Laura ; Caccialanza, Gabriele ; De Lorenzi, Ersilia. / CE can identify small molecules that selectively target soluble oligomers of amyloid β protein and display antifibrillogenic activity. In: Electrophoresis. 2009 ; Vol. 30, No. 8. pp. 1418-1429.
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