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 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.
Department of General Biophysics, University of Lodz, Poland.
Tomasz
T
Wasiak
Maksim
M
Ionov
Krzysztof
K
Nieznanski
Hanna
H
Nieznanska
Oxana
O
Klementieva
Maritxell
M
Granell
Josep
J
Cladera
Jean-Pierre
JP
Majoral
Anne Marie
AM
Caminade
Barbara
B
Klajnert
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010758:Phosphorus / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry; D016875:tau Proteins / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D050091:Dendrimers; D016875:tau Proteins; D010758:Phosphorus; D014443:Tyrosine