Phosphorus Dendrimers Affect Alzheimer’s (Aβ1–28) Peptide and MAP-Tau Protein Aggregation

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 pr...

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Bibliographic Details
Published in:Molecular pharmaceutics 2012-03, Vol.9 (3), p.458-469
Main Authors: Wasiak, Tomasz, Ionov, Maksim, Nieznanski, Krzysztof, Nieznanska, Hanna, Klementieva, Oxana, Granell, Maritxell, Cladera, Josep, Majoral, Jean-Pierre, Caminade, Anne Marie, Klajnert, Barbara
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - ultrastructure
Animals
Cell Line, Tumor
Circular Dichroism
Dendrimers - chemistry
Humans
Mice
Microscopy, Electron, Transmission
Phosphorus - chemistry
tau Proteins - chemistry
Tyrosine - chemistry
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Summary: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 (Aβ1–28) 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 Aβ1–28 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.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp2005627