A VEGF Fragment Encompassing Residues 10-30 Inhibits Aβ1-42 Amyloid Aggregation and Exhibits Neuroprotective Properties Matching the Full-Length Protein.

The intricate relationship between brain vascular diseases and neurodegeneration has garnered increased attention in the scientific community. With an aging population, the incidence of these two conditions is likely to increase, making it imperative to understand the underlying common molecular mechanisms and unveiling novel avenues for therapy. Prompted by the observation that Aβ peptide aggregation has been implicated in the development of cerebral amyloid angiopathy (CAA) and that elevated concentrations of vascular endothelial growth factor (VEGF) in the cerebrospinal fluid (CSF) have been correlated with less cognitive decline in Alzheimer's disease (AD), we demonstrate that a small peptide (Pep9) encompassing the 10-30 sequence of VEGF exhibits significant ability to inhibit the aggregation of the Aβ1-42 peptide, as well as the formation of toxic oligomers.

α-Casein-Loaded Proteo-liposomes as Potential Inhibitors in Amyloid Fibrillogenesis: Effects on a Model of Alzheimer's Disease.

According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid β-peptide (Aβ) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria.

Small Angle X-ray Scattering Sensing Membrane Composition: The Role of Sphingolipids in Membrane-Amyloid β-Peptide Interaction.

The early impairments appearing in Alzheimer's disease are related to neuronal membrane damage. Both aberrant Aβ species and specific membrane components play a role in promoting aggregation, deposition, and signaling dysfunction. Ganglioside GM1, present with cholesterol and sphingomyelin in lipid rafts, preferentially interacts with the Aβ peptide.

Nanoalgosomes: Introducing extracellular vesicles produced by microalgae.

Cellular, inter-organismal and cross kingdom communication via extracellular vesicles (EVs) is intensively studied in basic science with high expectation for a large variety of bio-technological applications. EVs intrinsically possess many attributes of a drug delivery vehicle. Beyond the implications for basic cell biology, academic and industrial interests in EVs have increased in the last few years.

Isolation of extracellular vesicles from microalgae: towards the production of sustainable and natural nanocarriers of bioactive compounds.

Safe, efficient and specific nano-delivery systems are essential for current and emerging therapeutics, precision medicine and other biotechnology sectors. Novel bio-based nanotechnologies have recently arisen, which are based on the exploitation of extracellular vesicles (EVs). In this context, it has become essential to identify suitable organisms or cellular types to act as reliable sources of EVs and to develop their pilot- to large-scale production.

Light Scattering as an Easy Tool to Measure Vesicles Weight Concentration.

Over the last few decades, liposomes have emerged as promising drug delivery systems and effective membrane models for studying biophysical and biological processes. For all applications, knowing their concentration after preparation is crucial. Thus, the development of methods for easily controlling vesicles concentration would be of great utility.

Inhibition of Aβ Fibrillation by Chaperonins: Human Hsp60 Is a Stronger Inhibitor than Its Bacterial Homologue GroEL.

Alzheimer's disease is a chronic neurodegenerative disease characterized by the accumulation of pathological aggregates of amyloid beta peptide. Many efforts have been focused on understanding peptide aggregation pathways and on identification of molecules able to inhibit aggregation in order to find an effective therapy. As a result, interest in neuroprotective proteins, such as molecular chaperones, has increased as their normal function is to assist in protein folding or to facilitate the disaggregation and/or clearance of abnormal aggregate proteins.

Amyloid β-Peptide Interaction with Membranes: Can Chaperones Change the Fate?

The understanding of amyloid β-peptide (Aβ) interactions with cellular membranes is a crucial molecular challenge against Alzheimer's disease. Indeed, Aβ prefibrillar oligomeric intermediates are believed to be the most toxic species, able to induce cellular damages directly by membrane damage. We present a neutron-scattering study on the interaction of large unilamellar vesicles (LUV), as cell membrane models, with both freshly dissolved Aβ and early toxic prefibrillar oligomers, intermediate states in the amyloid pathway.

Biophysical characterization of asolectin-squalene liposomes.

Liposomes are shell nanoparticles able to embed hydrophobic molecules into their lipid layers to be released to cells. In pharmaceutical sciences, liposomes remain the delivery system with the highest biocompatibility, stability, loading characteristics, tunable physicochemical properties. Squalene is a natural, water insoluble, lipid, abundant in olive oil and shark liver.

The effects of pressure on the energy landscape of proteins.

Protein dynamics is characterized by fluctuations among different conformational substates, i.e. the different minima of their energy landscape.

Investigation on different chemical stability of mitochondrial Hsp60 and its precursor.

In the large class of molecules that maintain protein homeostasis, called molecular chaperones, chaperonins constitute a subclass that specifically assist the correct folding of newly synthesized proteins. Among them, Hsp60 is composed of a double heptameric ring structure with a large central cavity where the unfolded protein binds via hydrophobic interactions and is supported, in this function, by the co-chaperonin Hsp10. Hsp60 is typically located in the mitochondria, but in some pathological situations, such as cancers and chronic inflammatory diseases, Hsp60 accumulates in the cytoplasm.

α-Casein Inhibits Insulin Amyloid Formation by Preventing the Onset of Secondary Nucleation Processes.

α-Casein is known to inhibit the aggregation of several proteins, including the amyloid β-peptide, by mechanisms that are not yet completely clear. We studied its effects on insulin, a system extensively used to investigate the properties of amyloids, many of which are common to all proteins and peptides. In particular, as for other proteins, insulin aggregation is affected by secondary nucleation pathways.

Stability and disassembly properties of human naïve Hsp60 and bacterial GroEL chaperonins.

Human Hsp60 chaperonin and its bacterial homolog GroEL, in association with the corresponding co-chaperonins Hsp10 and GroES, constitute important chaperone systems promoting the proper folding of several mitochondrial proteins. Hsp60 is also currently described as a ubiquitous molecule with multiple roles both in health conditions and in several diseases. Naïve Hsp60 bearing the mitochondrial import signal has been recently demonstrated to present different oligomeric organizations with respect to GroEL, suggesting new possible physiological functions.

Amyloid β-peptide insertion in liposomes containing GM1-cholesterol domains.

Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid β-peptide (Aβ) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate Aβ aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between Aβ and liposomes, a good membrane model system.

Human Hsp60 with its mitochondrial import signal occurs in solution as heptamers and tetradecamers remarkably stable over a wide range of concentrations.

It has been established that Hsp60 can accumulate in the cytosol in various pathological conditions, including cancer and chronic inflammatory diseases. Part or all of the cytosolic Hsp60 could be naïve, namely, bear the mitochondrial import signal (MIS), but neither the structure nor the in solution oligomeric organization of this cytosolic molecule has still been elucidated. Here we present a detailed study of the structure and self-organization of naïve cytosolic Hsp60 in solution.

Different effects of Alzheimer's peptide Aβ(1-40) oligomers and fibrils on supported lipid membranes.

Beta-amyloid (1-40) is one of the two most abundant species of amyloid-beta peptides present as fibrils in the extracellular senile plaques in the brain of Alzheimer's patients. Recently, the molecular aggregates constituting the early stage of fibril formation, i.e.

α-Casein inhibition mechanism in concanavalin A aggregation process.

The inhibition of the aggregation in protein solutions is currently a subject of great interest in many research fields, from the study of protein-misfolding related diseases to pharmaceutics, biotechnology, and food science. α(s1)-Casein, one of the four types of caseins, which are the largest protein component of bovine milk, has been found to hinder the aggregation process of several proteins, including the amyloid β-peptide, involved in Alzheimer's disease. To shed light into the mechanisms by which casein exerts this chaperon-like protective action, we studied its effect on the different steps of the aggregation process of concanavalin A, by means of both static and dynamic light scattering, thioflavin T and ANS fluorescence, circular dichroism, and atomic force microscopy.

Insulin-activated Akt rescues Aβ oxidative stress-induced cell death by orchestrating molecular trafficking.

Increasing evidence indicates that Alzheimer's disease, one of the most diffused aging pathologies, and diabetes may be related. Here, we demonstrate that insulin signalling protects LAN5 cells by amyloid-β42 (Aβ)-induced toxicity. Aβ affects both activation of insulin receptors and the levels of phospho-Akt, a critical signalling molecule in this pathway.

Concanavalin A aggregation and toxicity on cell cultures.

A number of neurodegenerative diseases are known to involve protein aggregation. Common mechanisms and structural properties of amyloids are thought to be involved in aggregation-related cytotoxicity. In this context we propose an experimental study on Concanavalin A (Con A) aggregation and use it as a model to study the relationship between cell toxicity and aggregation processes.

Abeta oligomers and fibrillar aggregates induce different apoptotic pathways in LAN5 neuroblastoma cell cultures.

Fibril deposit formation of amyloid beta-protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Abeta oligomers, which have been found in soluble brain extracts of AD patients, rather than to insoluble fibers. Here we report a study of the toxicity of two distinct forms of recombinant Abeta small oligomers and fibrillar aggregates to simulate the action of diffusible Abeta oligomers and amyloid plaques on neuronal cells.

Protein stability modulated by a conformational effector: effects of trifluoroethanol on bovine serum albumin.

The link between the thermodynamic properties of a solution and the conformational space explored by a protein is of fundamental importance to understand and control solubility, misfolding and aggregation processes. Here, we study the thermodynamic and conformational stability of a model protein, bovine serum albumin (BSA), by addition of trifluoroethanol (TFE), which is known to affect both the solvent properties and the protein structure. The solvent-mediated pair-wise interactions are investigated by static and dynamic light scattering, and by small angle X-ray scattering.

Large size fibrillar bundles of the Alzheimer amyloid beta-protein.

Self-assembly of amyloid beta-protein (Abeta) and its deposition into senile plaques are distinctive features of Alzheimer's disease. Abeta forms typical linear aggregates known as amyloid fibrils, with a diameter of a few tens of nanometers and a length spanning from hundreds of nanometers to micrometers. Fibrils eventually assemble into large size clusters and precipitate in vivo in the brain deposits.

Employment of cationic solid-lipid nanoparticles as RNA carriers.

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. In this article, the suitability of cationically modified solid-lipid nanoparticles (SLN) as a nonviral vector for gene delivery was investigated, in order to obtain stable materials able to condense RNA. Cationic SLN were produced by microemulsion using Compritol ATO 888 as matrix lipid, Pluronic F68 as tenside, and dimethyldioctadecylammonium bromide (DDAB) as cationic lipid.

Kinetics of different processes in human insulin amyloid formation.

Human insulin has long been known to form amyloid fibrils under given conditions. The molecular basis of insulin aggregation is relevant for modeling the amyloidogenesis process, which is involved in many pathologies, as well as for improving delivery systems, used for diabetes treatments. Insulin aggregation displays a wide variety of morphologies, from small oligomeric filaments to huge floccules, and therefore different specific processes are likely to be intertwined in the overall aggregation.

Protofibril formation of amyloid beta-protein at low pH via a non-cooperative elongation mechanism.

Deposition of the amyloid beta-protein (Abeta) in senile or diffuse plaques is a distinctive feature of Alzheimer's disease. The role of Abeta aggregates in the etiology of the disease is still controversial. The formation of linear aggregates, known as amyloid fibrils, has been proposed as the onset and the cause of pathological deposition.