Tau-peptide fragments and their copper(II) complexes: Effects on Amyloid-beta aggregation(545 views) Di Natale G, Bellia F, Sciacca F, Campagna T, Pappalardo G
Tau-peptide fragments and their copper(II) complexes: Effects on Amyloid-beta aggregation
Recent studies suggest that the interaction of Aβ and Tau may be
significant in the pathogenesis of Alzheimer’s diseases (AD). In
addition, the potential influence of copper on Tau-related pathology in
AD has not been previously addresseded and the interaction between Tau
protein, Aβ and copper has even more recently been associated with AD.
While the copper(II) interaction with the Aβ peptide has exhaustively
been studied, the few studies carried out on copper(II) complexes with
peptide fragments from Tau protein have been focused on the
pseudo-repeats of Tau protein in the microtubule-binding region. No data
have been reported about the metal complexes with peptides derived from
the
N
-terminal portion of Tau protein, outside the
microtubule-binding domain, despite increased levels of peptide
fragments from this region have been detected in the Cerebrospinal fluid
(CSF) of AD patients. Here we examine the interaction of two peptides
fragments, encompassing the 1–25 or 26–44 residues of the human Tau
protein sequence, with Aβ as well as the Cu
2+
-binding
features of these two naturally occurring peptides. The CD experiments
showed that copper(II) differently affects the peptide conformation of
the two ligands and provided also insight into the donor atoms involved
in metal coordination. Stoichiometry of copper(II) complexes was
obtained by means of High resolution ESI-MS. Finally, the influence of
the studied peptide on Aβ’s fibrillogenesis, either in the presence or
absence of Cu
2+
, was investigated by means of Th-T fluorescence coupled with turbidimetric measurements. The observed different effect on the
in vitro
Aβ’s aggregation, was correlated with the affinity of copper(II) with
the two peptide ligands. The overall results indicate that copper(II)
can bind these peptides using the histidine residue or amino group as
anchoring sites and that copper(II) binding may have a possible
involvement in AD.
Tau-peptide fragments and their copper(II) complexes: Effects on Amyloid-beta aggregation
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(659 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote