Phosphorus dendrimers affect Alzheimer's (Aβ <inf>1-28</inf>) peptide and MAP-Tau protein aggregation

Tomasz Wasiak, Maksim Ionov, Krzysztof Nieznanski, Hanna Nieznanska, Oxana Klementieva, Maritxell Granell, Josep Cladera, Jean Pierre Majoral, Anne Marie Caminade, Barbara Klajnert

Research output: Contribution to journalArticleResearchpeer-review

83 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by pathological aggregation of β-amyloid peptides and MAP-Tau protein. β-Amyloid (Aβ) is a peptide responsible for extracellular Alzheimer's plaque formation. Intracellular MAP-Tau aggregates appear as a result of hyperphosphorylation of this cytoskeletal protein. Small, oligomeric forms of Aβ are intermediate products that appear before the amyloid plaques are formed. These forms are believed to be most neurotoxic. Dendrimers are highly branched polymers, which may find an application in regulation of amyloid fibril formation. Several biophysical and biochemical methods, like circular dichroism (CD), fluorescence intensity of thioflavin T and thioflavin S, transmission electron microscopy, spectrofluorimetry (measuring quenching of intrinsic peptide fluorescence) and MTT-cytotoxicity assay, were applied to characterize interactions of cationic phosphorus-containing dendrimers of generation 3 and generation 4 (CPDG3, CPDG4) with the fragment of amyloid peptide (Aβ 1 - 28) and MAP-Tau protein. We have demonstrated that CPDs are able to affect β-amyloid and MAP-Tau aggregation processes. A neuro-2a cell line (N2a) was used to test cytotoxicity of formed fibrils and intermediate products during the Aβ 1 - 28 aggregation. It has been shown that CPDs might have a beneficial effect by reducing the system toxicity. Presented results suggest that phosphorus dendrimers may be used in the future as agents regulating the fibrilization processes in Alzheimer's disease. © 2011 American Chemical Society.
Original languageEnglish
Pages (from-to)458-469
JournalMolecular Pharmaceutics
Volume9
Issue number3
DOIs
Publication statusPublished - 5 Mar 2012

Keywords

  • β-amyloid
  • aggregation
  • amyloid peptide
  • cytotoxicity
  • fibril formation
  • MAP-Tau protein
  • phosphorus dendrimers
  • ThS assay
  • ThT assay

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