0000000000374588
AUTHOR
Paolo De Bona
Beta-amyloid monomers are neuroprotective
The 42-aa-long β-amyloid protein—Aβ1-42—is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Aβ peptides (Lambert et al., 1998) indicate that self-association of Aβ1-42monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Aβ1-42is unknown. The evidence that Aβ1-42is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Aβ1-42monomers support …
Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Aβ(1-42) fibrillogenesis and toxicity
Aggregation of the amyloid A? peptide and its accumulation into insoluble deposits (plaques) are believed to be the main cause of neuronal dysfunction associated with Alzheimer's disease (AD); small molecules that can interfere with the A? amyloid fibril formation are therefore of interest for a potential therapeutic strategy. Three new trehalose-conjugated peptides of the well known ?-sheet breaker peptide iA?5p,were synthesized. The disaccharide was covalently attached to different sites of the LPFFD peptide chain, i.e. at the N-terminus, C-terminus or at the Asp side chain. CD spectroscopy in different solvents was used to assess changes in the peptide conformation of these compounds. Th…
Copper(ii) and zinc(ii) dependent effects on Aβ42 aggregation: a CD, Th-T and SFM study
A? aggregation is a central event in Alzheimer's disease (AD). In vitro evidence indicates that A? aggregation and fibrillogenesis are significantly influenced by the employed experimental conditions. Indeed, although it is widely established that metal ions, such as copper and zinc, have significant effects on the A? aggregation process, their actual role in A? fibrillogenesis is still debated. In this work the effects of a molar excess of zinc(ii) and/or copper(ii) ions on the A?42 aggregation process and the morphology of the resultant aggregates have been compared in samples exhibiting different initial conformations. CD spectroscopy, Th-T-induced fluorescence and Scanning Force Microsc…