Mixing Aβ(1-40) and Aβ(1-42) peptides generates unique amyloid fibrils.

Recent structural studies show distinct morphologies for the fibrils of Aβ(1-42) and Aβ(1-40), which are believed not to co-fibrillize. We describe here a novel, structurally-uniform 1 : 1 mixed fibrillar species, which differs from both pure fibrils. It forms preferentially even when Aβ(1-42) : Aβ(1-40) peptides are mixed in a non-stoichiometric ratio.

Interaction of Half Oxa-/Half -Platin Complex with Human Superoxide Dismutase and Induced Reduction of Neurotoxicity.

The formation of amorphous protein aggregates containing human superoxide dismutase (hSOD1) is thought to be involved in amyotrophic lateral sclerosis onset. -Platin inhibits the oligomerization of apo hSOD1, but its toxicity precludes any possible use in therapy. Herein, we propose a less toxic platinum complex, namely oxa/-platin, as hSOD1 antiaggregation lead compound.

Beta Amyloid Hallmarks: From Intrinsically Disordered Proteins to Alzheimer's Disease.

Beta amyloid protein (Aβ) is one of the intrinsically disordered proteins associated with neurodegenerative diseases like Parkinson's, prion disease and Alzheimer's disease (AD) in particular. Although the direct involvement of Aβ peptides in AD is well documented and their aggregative ability is closely related to their neurotoxicity, the precise mechanism of the neurotoxic effects of Aβ peptides remains unclear. There is still a significant gap between the site-specific structural information and the complex structural diversity of Aβ amyloids.

Recombinant Intrinsically Disordered Proteins for NMR: Tips and Tricks.

The growing recognition of the several roles that intrinsically disordered proteins play in biology places an increasing importance on protein sample availability to allow the characterization of their structural and dynamic properties. The sample preparation is therefore the limiting step to allow any biophysical method being able to characterize the properties of an intrinsically disordered protein and to clarify the links between these properties and the associated biological functions. An increasing array of tools has been recruited to help prepare and characterize the structural and dynamic properties of disordered proteins.

Formation kinetics and structural features of Beta-amyloid aggregates by sedimented solute NMR.

The accumulation of soluble toxic beta-amyloid (Aβ) aggregates is an attractive hypothesis for the role of this peptide in the pathology of Alzheimer's disease. We have introduced sedimentation through ultracentrifugation, either by magic angle spinning (in situ) or preparative ultracentrifuge (ex situ), to immobilize biomolecules and make them amenable for solid-state NMR studies (SedNMR). In situ SedNMR is used here to address the kinetics of formation of soluble Aβ assemblies by monitoring the disappearance of the monomer and the appearance of the oligomers simultaneously.