(Re)building the nervous system: A review of neuron-glia interactions from development to disease.

Neuron-glia interactions are fundamental to the development and function of the nervous system. During development, glia, including astrocytes, microglia, and oligodendrocytes, influence neuronal differentiation and migration, synapse formation and refinement, and myelination. In the mature brain, glia are crucial for maintaining neural homeostasis, modulating synaptic activity, and supporting metabolic functions.

Impact of Antioxidants on Mechanical Properties and ROS Levels of Neuronal Cells Exposed to β-Amyloid Peptide.

This study aims to investigate the potential role of antioxidants in oxidative stress and its consequent impact on the mechanical properties of neuronal cells, particularly the stress induced by amyloid-beta (1-42) (Aβ) aggregates. A key aspect of our research involved using scanning ion-conductance microscopy (SICM) to assess the mechanical properties (Young's modulus) of neuronal cells under oxidative stress. Reactive oxygen species (ROS) level was measured in single-cell using the electrochemical method by low-invasive Pt nanoelectrode.

Beta-Amyloid and Its Asp7 Isoform: Morphological and Aggregation Properties and Effects of Intracerebroventricular Administration.

Background/objectives: One of the hallmarks of Alzheimer's disease (AD) is the accumulation of aggregated beta-amyloid (Aβ) protein in the form of senile plaques within brain tissue. Senile plaques contain various post-translational modifications of Aβ, including prevalent isomerization of Asp7 residue. The Asp7 isomer has been shown to exhibit increased neurotoxicity and induce amyloidogenesis in brain tissue of transgenic mice.

Post-translational modifications of beta-amyloid alter its transport in the blood-brain barrier model.

One of the hallmarks of Alzheimer's disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues.

Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.

The pathogenesis of Alzheimer's disease (AD) is associated with the formation of cerebral amyloid plaques, the main components of which are the modified Aβ molecules as well as the metal ions. Aβ isomerized at Asp7 residue (isoD7-Aβ) is the most abundant isoform in amyloid plaques. We hypothesized that the pathogenic effect of isoD7-Aβ is due to the formation of zinc-dependent oligomers, and that this interaction can be disrupted by the rationally designed tetrapeptide (HAEE).

Phosphorylation and Dephosphorylation of Beta-Amyloid Peptide in Model Cell Cultures: The Role of Cellular Protein Kinases and Phosphatases.

Phosphorylation of beta-amyloid peptide (Aβ) at the Ser8 residue affects its neurotoxicity, metal-dependent oligomerisation, amyloidogenicity, and other pathogenic properties. Phosphorylated Aβ (pS8-Aβ) was detected in vivo in AD model mice and in the brains of patients with AD. However, the pS8-Aβ production and the regulation of its levels have not been previously studied in detail.

Distinct Effects of Beta-Amyloid, Its Isomerized and Phosphorylated Forms on the Redox Status and Mitochondrial Functioning of the Blood-Brain Barrier Endothelium.

The Alzheimer's disease (AD)-associated breakdown of the blood-brain barrier (BBB) promotes the accumulation of beta-amyloid peptide (Aβ) in the brain as the BBB cells provide Aβ transport from the brain parenchyma to the blood, and vice versa. The breakdown of the BBB during AD may be caused by the emergence of blood-borne Aβ pathogenic forms, such as structurally and chemically modified Aβ species; their effect on the BBB cells has not yet been studied. Here, we report that the effects of Aβ, Aβ, containing isomerized Asp7 residue (iso-Aβ) or phosphorylated Ser8 residue (p-Aβ) on the mitochondrial potential and respiration are closely related to the redox status changes in the mouse brain endothelial cells bEnd.

Synthetic, Cell-Derived, Brain-Derived, and Recombinant β-Amyloid: Modelling Alzheimer's Disease for Research and Drug Development.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, characterised by the accumulation of senile plaques and tau tangles, neurodegeneration, and neuroinflammation in the brain. The development of AD is a pathological cascade starting according to the amyloid hypothesis with the accumulation and aggregation of the β-amyloid peptide (Aβ), which induces hyperphosphorylation of tau and promotes the pro-inflammatory activation of microglia leading to synaptic loss and, ultimately, neuronal death. Modelling AD-related processes is important for both studying the molecular basis of the disease and the development of novel therapeutics.

[Blood-Brain Barrier Transwell Modeling].

In vitro blood-brain barrier (BBB) modeling with the use of the brain endothelial cells grown on a transwell membrane is widely used to investigate BBB disorders and factors intended to ameliorate these pathologies. Endothelial cells, due to tight junction proteins, ensure selective permeability for a number of substances. The low integrity (i.

Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation.

Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer's disease and as a regulator in brain physiology. The inhibitory effect of Aβ oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer's disease. Still, the physiological role of the monomeric form of Aβ interaction with Na,K-ATPase remains unclear.

Snake Toxins Labeled by Green Fluorescent Protein or Its Synthetic Chromophore are New Probes for Nicotinic acetylcholine Receptors.

Fluorescence can be exploited to monitor intermolecular interactions in real time and at a resolution up to a single molecule. It is a method of choice to study ligand-receptor interactions. However, at least one of the interacting molecules should possess good fluorescence characteristics, which can be achieved by the introduction of a fluorescent label.

Tetrapeptide Ac-HAEE-NH Protects α4β2 nAChR from Inhibition by Aβ.

The cholinergic deficit in Alzheimer's disease (AD) may arise from selective loss of cholinergic neurons caused by the binding of Aβ peptide to nicotinic acetylcholine receptors (nAChRs). Thus, compounds preventing such an interaction are needed to address the cholinergic dysfunction. Recent findings suggest that the EVHH site in Aβ peptide mediates its interaction with α4β2 nAChR.

Isomerization of Asp7 in Beta-Amyloid Enhances Inhibition of the α7 Nicotinic Receptor and Promotes Neurotoxicity.

Cholinergic dysfunction in Alzheimer's disease (AD) can be mediated by the neuronal α7 nicotinic acetylcholine receptor (α7nAChR). Beta-amyloid peptide (Aβ) binds to the α7nAChR, disrupting the receptor's function and causing neurotoxicity. In vivo not only Aβ but also its modified forms can drive AD pathogenesis.

Anti-amyloid Therapy of Alzheimer's Disease: Current State and Prospects.

Drug development for the treatment of Alzheimer's disease (AD) has been for a long time focused on agents that were expected to support endogenous β-amyloid (Aβ) in a monomeric state and destroy soluble Aβ oligomers and insoluble Aβ aggregates. However, this strategy has failed over the last 20 years and was eventually abandoned. In this review, we propose a new approach to the anti-amyloid AD therapy based on the latest achievements in understanding molecular causes of cerebral amyloidosis in AD animal models.

Phosphorylation of the Amyloid-Beta Peptide Inhibits Zinc-Dependent Aggregation, Prevents Na,K-ATPase Inhibition, and Reduces Cerebral Plaque Deposition.

The triggers of late-onset sporadic Alzheimer's disease (AD) are still poorly understood. Impairment of protein phosphorylation with age is well-known; however, the role of the phosphorylation in β-amyloid peptide (Aβ) is not studied sufficiently. Zinc-induced oligomerization of Aβ represents a potential seeding mechanism for the formation of neurotoxic Aβ oligomers and aggregates.

Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer's Disease.

Cerebral β-amyloidosis, an accumulation in the patient's brain of aggregated amyloid-β (Aβ) peptides abnormally saturated by divalent biometal ions, is one of the hallmarks of Alzheimer's disease (AD). Earlier, we found that exogenously administrated synthetic Aβ with isomerized Asp7 (isoD7-Aβ) induces Aβ fibrillar aggregation in the transgenic mice model of AD. IsoD7-Aβ molecules have been implied to act as seeds enforcing endogenous Aβ to undergo pathological aggregation through zinc-mediated interactions.

[Isomerization of Asp7 increases the toxic effects of amyloid β and its phosphorylated form in SH-SY5Y neuroblastoma cells].

The generation of amyloid β (Aβ) toxic oligomers during the formation of senile plaques and amyloid fibrils is thought to play a central role in the onset and progression of Alzheimer's disease. Aβ production is a physiological process, but the factors that trigger a transition to pathogenic Aβ aggregation remain unknown. Posttranslational modifications of Aβ could potentially induce the transition.

[Heat-shock protein HSP70 protects neuroblastoma cells SK-N-SH from the neurotoxic effects hydrogen peroxide and the β-amyloid peptide].

Neuronal cell death in Alzheimer's disease is associated with the development of oxidative stress caused by the reactive oxygen species (ROS), which can be generated as a result of the effect of beta-amyloid peptides. One of the sources of ROS is hydrogen peroxide, inducing the apoptosis and necrosis of neural tissue cells. The mechanism of hydrogen peroxide apoptotic action includes launching signaling pathways that involve protein kinases PI3K, p38MAPK, JNK and ERK.