Brain penetration of peripheral extracellular vesicles from Alzheimer's patients and induction of microglia activation.

Alzheimer's disease (AD) is an age-related neurodegenerative pathology. Brain-derived extracellular vesicles (EVs) have been demonstrated to be implicated in AD pathogenesis by facilitating the propagation of Tau, amyloid-β and inflammatory cytokines. However, the impact of peripheral EVs (pEVs) in AD pathogenesis remains poorly investigated.

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy.

Persistent reactive oxygen species (ROS) and neuroinflammation contribute to the onset and progression of neurodegenerative diseases, underscoring the need for targeted therapeutic strategies to mitigate these effects. Extracellular vesicles (EVs) show promise in drug delivery due to their biocompatibility, ability to cross biological barriers, and specific interactions with cell and tissue receptors. In this study, we demonstrated that human plasma-derived EVs (pEVs) exhibit higher brain-targeting specificity, while adipose-derived mesenchymal stem cells EVs (ADMSC-EVs) offer regenerative and immunomodulatory properties.

In Vitro Assessment of the Neuroprotective Effects of Pomegranate ( L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress.

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer's disease (AD).

Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and aril extracts).

Methods: We used flow cytometry to quantify the protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific marker (CD86 and CD163) expression in human microglia HMC3 cells.

Synthesis and pharmacological evaluation of nature-inspired phenacyl glycosides.

Phenylethanoid glycosides are a well-studied class of bioactive compounds found throughout the plant kingdom. In contrast, research on the synthesis and pharmacological activity of phenacyl glycosides, a specific subgroup of phenylethanoid glycosides with a ketone functionality at the alpha position of the phenol ring, has been limited. In this study, we report the synthesis, cytotoxic, antiviral, and anti-inflammatory evaluation of a series of 18 4'-hydroxyphenacyl glycosides.

Implication of Circulating Extracellular Vesicles-Bound Amyloid-β42 Oligomers in the Progression of Alzheimer's Disease.

Background: The perplex interrelation between circulating extracellular vesicles (cEVs) and amyloid-β (Aβ) deposits in the context of Alzheimer's disease (AD) is poorly understood.

Objective: This study aims to 1) analyze the possible cross-linkage of the neurotoxic amyloid-β oligomers (oAβ) to the human cEVs, 2) identify cEVs corona proteins associated with oAβ binding, and 3) analyze the distribution and expression of targeted cEVs proteins in preclinical participants converted to AD 5 years later (Pre-AD).

Methods: cEVs were isolated from 15 Pre-AD participants and 15 healthy controls selected from the Canadian Study of Health and Aging.

Viruses - a major cause of amyloid deposition in the brain.

Introduction: Clinically, Alzheimer's disease (AD) is a syndrome with a spectrum of various cognitive disorders. There is a complete dissociation between the pathology and the clinical presentation. Therefore, we need a disruptive new approach to be able to prevent and treat AD.

Deep Tissue Penetration of Bottle-Brush Polymers via Cell Capture Evasion and Fast Diffusion.

Drug nanocarriers (NCs) capable of crossing the vascular endothelium and deeply penetrating into dense tissues of the CNS could potentially transform the management of neurological diseases. In the present study, we investigated the interaction of bottle-brush (BB) polymers with different biological barriers and and compared it to nanospheres of similar composition. internalization and permeability assays revealed that BB polymers are not internalized by brain-associated cell lines and translocate much faster across a blood-brain barrier model compared to nanospheres of similar hydrodynamic diameter.

Interaction Mechanism Between the HSV-1 Glycoprotein B and the Antimicrobial Peptide Amyloid-β.

Background: Unravelling the mystery of Alzheimer's disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the amyloid-β peptide (Aβ) and the intracellular neurofibrillary tangles could occur within the brain without any cognitive pathology.

In Situ Characterization of the Protein Corona of Nanoparticles In Vitro and In Vivo.

A new theoretical framework that enables the use of differential dynamic microscopy (DDM) in fluorescence imaging mode to quantify in situ protein adsorption onto nanoparticles (NP) while simultaneously monitoring for NP aggregation is proposed. This methodology is used to elucidate the thermodynamic and kinetic properties of the protein corona (PC) in vitro and in vivo. The results show that protein adsorption triggers particle aggregation over a wide concentration range and that the formed aggregate structures can be quantified using the proposed methodology.

Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity.

The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism.

Effect of ε4 allele on levels of apolipoproteins E, J, and D, and redox signature in circulating extracellular vesicles from cognitively impaired with no dementia participants converted to Alzheimer's disease.

Introduction: The substantial link between apolipoprotein E () ε4 allele and oxidative stress may underlie enhanced Alzheimer's disease (AD) risk. Here, we studied the impact of ε4 on the level of apolipoproteins with antioxidant activities along with oxidative markers in circulating extracellular vesicles (cEVs) and plasma from cognitively impaired-not demented (CIND) individuals converted to AD (CIND-AD).

Methods: Apolipoproteins E, J, and D and antioxidant response markers were determined in cEVs and plasma using immunoblotting, electrochemical examination, and spectrofluorimetry.

Levels of Receptor for Advanced Glycation End Products and Glyoxalase-1 in the Total Circulating Extracellular Vesicles from Mild Cognitive Impairment and Different Stages of Alzheimer's Disease Patients.

Background: Growing evidence supports that receptor for advanced glycation end products (RAGE) and glyoxalase-1 (GLO-1) are implicated in the pathophysiology of Alzheimer's disease (AD). Extracellular vesicles (EVs) are nanovesicles secreted by almost all cell types, contribute to cellular communication, and are implicated in AD pathology. Recently, EVs are considered as promising tools to identify reliable biomarkers in AD.

Nanoparticle shell structural cues drive in vitro transport properties, tissue distribution and brain accessibility in zebrafish.

Zwitterion polymers with strong antifouling properties have been suggested as the prime alternative to polyethylene glycol (PEG) for drug nanocarriers surface coating. It is believed that PEG coating shortcomings, such as immune responses and incomplete protein repellency, could be overcome by zwitterionic polymers. However, no systematic study has been conducted so far to complete a comparative appraisal of PEG and zwitterionic-coating effects on nanoparticles (NPs) stealthness, cell uptake, cell barrier translocation and biodistribution in the context of nanocarriers brain targeting.

Corilagin and 1,3,6-Tri--galloy-β-D-glucose: potential inhibitors of SARS-CoV-2 variants.

The COVID-19 disease caused by the virus SARS-CoV-2, first detected in December 2019, is still emerging through virus mutations. Although almost under control in some countries due to effective vaccines that are mitigating the worldwide pandemic, the urgency to develop additional vaccines and therapeutic treatments is imperative. In this work, the natural polyphenols corilagin and 1,3,6-tri-O-galloy-β-d-glucose (TGG) are investigated to determine the structural basis of inhibitor interactions as potential candidates to inhibit SARS-CoV-2 viral entry into target cells.

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD.

Cerebral Apolipoprotein D Exits the Brain and Accumulates in Peripheral Tissues.

Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. In rodent, the bulk of its expression occurs in the central nervous system. Despite this, ApoD has profound effects in peripheral tissues, indicating that neural ApoD may reach peripheral organs.

Polyphenol-Peptide Interactions in Mitigation of Alzheimer's Disease: Role of Biosurface-Induced Aggregation.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, responsible for nearly two-thirds of all dementia cases. In this review, we report the potential AD treatment strategies focusing on natural polyphenol molecules (green chemistry) and more specifically on the inhibition of polyphenol-induced amyloid aggregation/disaggregation pathways: in bulk and on biosurfaces. We discuss how these pathways can potentially alter the structure at the early stages of AD, hence delaying the aggregation of amyloid-β (Aβ) and tau.

Glutathione: An Old and Small Molecule with Great Functions and New Applications in the Brain and in Alzheimer's Disease.

Glutathione (GSH) represents the most abundant and the main antioxidant in the body with important functions in the brain related to Alzheimer's disease (AD). Oxidative stress is one of the central mechanisms in AD. We and others have demonstrated the alteration of GSH levels in the AD brain, its important role in the detoxification of advanced glycation end-products and of acrolein, a by-product of lipid peroxidation.

Apolipoprotein E4-driven effects on inflammatory and neurotrophic factors in peripheral extracellular vesicles from cognitively impaired, no dementia participants who converted to Alzheimer's disease.

Introduction: In brain, extracellular vesicles (EVs) play an essential role in the neuron-glia interface and ensure the crosstalk between the brain and the periphery. Some studies now link the pathway dysfunction of the EVs to apolipoprotein E gene variant ( ε4) and the risk of progression to Alzheimer's disease (AD). To better understand the role of ε4 in pre-clinical AD, we have determined levels of pathogenic, neurotrophic and inflammatory proteins in peripheral EVs (pEVs) and in plasma from cognitively impaired, no dementia (CIND) participants stratified upon the absence ( ε4) or the presence ( ε4 ) of the ε4 allele of .

Isolation of Neuroprotective Anthocyanins from Black Chokeberry () against Amyloid-β-Induced Cognitive Impairment.

Black chokeberry () fruits are rich in anthocyanins, which are vital secondary metabolites that possess antioxidative properties. The aim of this study was to isolate and purify the anthocyanins from black chokeberry by simulated moving bed (SMB) chromatography, and to investigate the neuroprotective effect of SMB purified anthocyanin against Aβ-induced memory damage in rats. The parameters of the SMB process were studied and optimized.

Date seeds alleviate behavioural and neuronal complications of metabolic syndrome in rats.

Unhealthy dietary habits can play a crucial role in metabolic damages, promoting alteration of neural functions through the lifespan. Recently, dietary change has been perceived as the first line intervention in prevention and/or treatment of metabolic damages and related diseases. In this context, our study was designed to assess the eventual therapeutic effect of date seeds administration on memory and learning and on neuronal markers in a rat Metabolic Syndrome model.

Transport of PEGylated-PLA nanoparticles across a blood brain barrier model, entry into neuronal cells and in vivo brain bioavailability.

Treatments of neurodegenerative diseases (NDDs) are severely hampered by the presence of the blood-brain barrier (BBB) precluding efficient brain drug delivery. The development of drug nanocarriers aims at increasing the brain therapeutic index would represent a real progress in brain disease management. PEGylated polyester nanoparticles (NPs) are intensively tested in clinical trials for improved drug delivery.

Profile of pathogenic proteins in total circulating extracellular vesicles in mild cognitive impairment and during the progression of Alzheimer's disease.

Accumulating evidence suggests that the propagation of hyperphosphorylation of tau protein and the amyloid-β peptide can be mediated by extracellular vesicles (EVs) and be associated with the onset and the progression of Alzheimer's disease (AD). As EVs may transfer between the brain and the blood, we have thus hypothesized that the total plasma EVs (pEVs) may contain potential markers to predict the mild cognitive impairment (MCI) and AD progression. We have thus quantified AD-related proteins in isolated pEVs from controls, MCI and AD subjects.