Sebastiano Cataldo

β-Amyloid Monomers Are Neuroprotective

The 42-aa-long β-amyloid protein—Aβ1-42—is thought to play a central role in the pathogenesis of Alzheimers 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 Aβ1-42 monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Aβ1-42 is unknown. The evidence that Aβ1-42 is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Aβ1-42 monomers support the survival of developing neurons under conditions of trophic deprivation and protect mature neurons against excitotoxic death, a process that contributes to the overall neurodegeneration associated with AD. The neuroprotective action of Aβ1-42 monomers was mediated by the activation of the PI-3-K (phosphatidylinositol-3-kinase) pathway, and involved the stimulation of IGF-1 (insulin-like growth factor-1) receptors and/or other receptors of the insulin superfamily. Interestingly, monomers of Aβ1-42 carrying the Arctic mutation (E22G) associated with familiar AD (Nilsberth et al., 2001) were not neuroprotective. We suggest that pathological aggregation of Aβ1-42 may also cause neurodegeneration by depriving neurons of the protective activity of Aβ1-42 monomers. This “loss-of-function” hypothesis of neuronal death should be taken into consideration when designing therapies aimed at reducing Aβ burden.

Carbon nanotubes and organic solar cells

The use of carbon nanotubes in photovoltaics is still challenging due to different issues connected to their synthesis, purification, functionalization, processing and device integration. From this perspective at first we review on selected contributions dealing with the above issues; then we focus on the advantages and limitations of carbon nanotubes for the development of organic solar cells.

Organoboron Polymers for Photovoltaic Bulk Heterojunctions

We report on the application of three-coordinate organoboron polymers, inherently strong electron acceptors, in flexible photovoltaic (PV) cells. Poly[(1,4-divinylenephenylene)(2,4,6-triisopropylphenylborane)] (PDB) has been blended with poly(3-hexylthiophene-2,5-diyl) (P3HT) to form a thin film bulk heterojunction (BHJ) on PET/ITO substrates. Morphology may be modulated to give a high percentage of domains (10-20 nm in size) allowing exciton separation. The photoelectric properties of the BHJs in devices with aluminium back electrodes were imaged by light beam induced current (LBIC) and light beam induced voltage (LBIV) techniques. Open circuit voltages, short circuit currents and overall external quantum efficiencies obtained are among the highest reported for all-polymer PV cells.

Self-organization pathways and spatial heterogeneity in insulin amyloid fibril formation.

At high temperature and low pH, the protein hormone insulin is highly prone to form amyloid fibrils, and for this reason it is widely used as a model system to study fibril formation mechanisms. In this work, we focused on insulin aggregation mechanisms occurring in HCl solutions (pH 1.6) at 60 degrees C. By means of in situ Thioflavin T (ThT) staining, the kinetics profiles were characterized as a function of the protein concentration, and two concurrent aggregation pathways were pointed out, being concentration dependent. In correspondence to these pathways, different morphologies of self-assembled protein molecules were detected by atomic force microscopy images also evidencing the presence of secondary nucleation processes as a peculiar mechanism for insulin fibrillation. Moreover, combining ThT fluorescence and light scattering, the early stages of the process were analyzed in the low concentration regime, pointing out a pronounced spatial heterogeneity in the formation of the first stable fibrils in solution and the onset of the secondary nucleation pathways.

Carnosine Inhibits Aβ42 Aggregation by Perturbing the H‐Bond Network in and around the Central Hydrophobic Cluster

Aggregation of the amyloid‐β peptide (Aβ) into fibrillar structures is a hallmark of Alzheimers disease. Thus, preventing self‐assembly of the Aβ peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aβ aggregation. Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of Aβ42 but nonetheless inhibits amyloid growth. Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric Aβ42 by salt bridges with charged side chains, and van der Waals contacts with residues in and around the central hydrophobic cluster (17LVFFA21). NMR experiments on the nonaggregative fragment Aβ12–28 did not evidence specific intermolecular interactions between the peptide and carnosine, in agreement with MD simulations. However, a close inspection of the spectra revealed that carnosine interferes with the local propensity of the peptide to form backbone hydrogen bonds close to the central hydrophobic cluster (residues E22, S26 and N27). Finally, MD simulations of aggregation‐prone Aβ heptapeptide segments show that carnosine reduces the propensity to form intermolecular backbone hydrogen bonds in the region 18–24. Taken together, the experimental and simulation results (cumulative MD sampling of 0.2 ms) suggest that, despite the inability of carnosine to form stable contacts with Aβ, it might block the pathway toward toxic aggregates by perturbing the hydrogen bond network near residues with key roles in fibrillogenesis.

Protective Effects of L- and D-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease

Mildly denaturing conditions induce bovine alpha-crystallin, the major structural lens protein, to self-assemble into fibrillar structures in vitro. The natural dipeptide l-carnosine has been shown to have potential protective and therapeutic significance in many diseases. Carnosine derivatives have been proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. Here we report the inhibitory effect induced by the peptide (l- and d-enantiomeric form) on alpha-crystallin fibrillation and the almost complete restoration of the chaperone activity lost after denaturant and/or heat stress. Scanning force microscopy (SFM), thioflavin T, and a turbidimetry assay have been used to determine the morphology of alpha-crystallin aggregates in the presence and absence of carnosine. DSC and a near-UV CD assay evidenced that the structural precursors of amyloid fibrils are polypeptide chain segments that lack stable structural elements. Moreover, we have found a disassembling effect of carnosine on alpha-crystallin amyloid fibrils. Finally, we show the ability of carnosine to restore most of the lens transparency in organ-cultured rat lenses exposed to similar denaturing conditions that were used for the in vitro experiments.

Design and synthesis of new trehalose‐conjugated pentapeptides as inhibitors of Aβ(1–42) fibrillogenesis and toxicity

Aggregation of the amyloid Aβ peptide and its accumulation into insoluble deposits (plaques) are believed to be the main cause of neuronal dysfunction associated with Alzheimers disease (AD); small molecules that can interfere with the Aβ amyloid fibril formation are therefore of interest for a potential therapeutic strategy. Three new trehalose‐conjugated peptides of the well known β‐sheet breaker peptide iAβ5p, 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. The effects of these glycopeptides on the self‐assembly and morphology of Aβ aggregates were investigated by ThT fluorescence assay and dynamic Scanning Force Microscopy, respectively. All the synthesized compounds were tested as inhibitors of Aβ toxicity toward pure cultures of rat cortical neurons. Copyright

SPM and TOF-SIMS investigation of the physical and chemical modification induced by tip writing of self-assembled monolayers

Abstract The nanoelectrochemical modification of alkyl self-assembled monolayers (SAMs) obtained on hydrogenated silicon surfaces via radical-initiated reactions of 1-octadecene has been investigated. Scanning Probe Microscopy (SPM) showed that the modification of the organic layer occurs by applying either positive or negative biases to the tip at a threshold of about ±5 V. When the bias absolute value was ≤6 V, the height of the monolayer was only faintly modified, whereas a consistent increase in tip/sample friction force was observed, in agreement with the formation of hydrophilic moieties at the organic surface. In addition to the increase of friction, bias absolute values larger than 6 V led to a significant raise of the surface height, the application of negative biases resulting in stronger effects. This suggests the occurrence of a concomitant growth of silicon oxide underneath the organic layer. Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS) experiments, including chemical imaging and analysis of the retrospective spectra, were performed by writing patterns of some microns in size on the SAM. These experiments allowed to investigate the features of the chemical modification as a function of the applied bias. Positive spectra from the modified regions display the presence of C x H y O and C x H y N type peaks that increase with the tip bias, whereas an intensity reduction of the SiC x H y signals with respect to the unmodified regions was observed.

Polymeric Thin Films for Organic Electronics: Properties and Adaptive Structures

This review deals with the correlation between morphology, structure and performance of organic electronic devices including thin film transistors and solar cells. In particular, we report on solution processed devices going into the role of the 3D supramolecular organization in determining their electronic properties. A selection of case studies from recent literature are reviewed, relying on solution methods for organic thin-film deposition which allow fine control of the supramolecular aggregation of polymers confined at surfaces in nanoscopic layers. A special focus is given to issues exploiting morphological structures stemming from the intrinsic polymeric dynamic adaptation under non-equilibrium conditions.

Symmetric naphthalenediimidequaterthiophenes for electropolymerized electrochromic thin films

A new symmetric naphthalenediimidequaterthiophene (s-NDI2ODT4) was synthesized and exhibited the capability to electropolymerize alone or with EDOT affording polymers with controlled donor/acceptor monomer ratios. s-NDI2ODT4-EDOT-based copolymers showed low band gaps, wide optical absorption ranges extending to the near IR region, tuned electrical properties, thin-film surface morphology and hydrophilicity as well as high coloration efficiency in electrochromic devices.