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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Tomasz Wasiak
  • Maksim Ionov
  • Krzysztof Nieznanski
  • Hanna Nieznanska
  • Oxana Klementieva
  • Maritxell Granell
  • Josep Cladera
  • Jean Pierre Majoral
  • Anne Marie Caminade
  • Barbara Klajnert
External organisations
  • University of Lodz
  • Autonomous University of Barcelona
  • Nencki Institute of Experimental Biology of of the Polish Academy of Sciences
  • Laboratoire de Chimie de Coordination (LCC CNRS)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology
  • Medical Biotechnology

Keywords

  • β-amyloid, aggregation, amyloid peptide, cytotoxicity, fibril formation, MAP-Tau protein, phosphorus dendrimers, ThS assay, ThT assay
Original languageEnglish
Pages (from-to)458-469
Number of pages12
JournalMolecular Pharmaceutics
Volume9
Issue number3
Publication statusPublished - 2012 Mar 5
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes