ovalbumin and Alzheimer-Disease

Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease that affects the elderly. There is no ideal treatment for AD. Thus, the purpose of this study is to identify anti-AD peptides from ovalbumin.. The potential tripeptides IEK, LYR, and CIK were selected for molecular docking. The '-CDOCKER_Energy' values of the best docking positions of the tripeptide IEK, LYR, and CIK interacting with acetylcholinesterase (AChE) were 93.8119, 86.9556 and 73.6370 kcal mol. Tripeptide CIK can effectively inhibit the activities of AChE, BChE, and BACE1. Tripeptide CIK therefore has the potential to treat AD effectively. © 2020 Society of Chemical Industry.

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Butyrylcholinesterase; Cholinesterase Inhibitors; Molecular Docking Simulation; Ovalbumin; Peptides; Structure-Activity Relationship

Basement membranes in the walls of cerebral capillaries and arteries form a major lymphatic drainage pathway for fluid and solutes from the brain. Amyloid-β (Aβ) draining from the brain is deposited in such perivascular pathways as cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). CAA increases in severity when Aβ is removed from the brain parenchyma by immunotherapy for AD. In this study we investigated the consequences of immune complexes in artery walls upon drainage of solutes similar to soluble Aβ. We tested the hypothesis that, following active immunization with ovalbumin, immune complexes form within the walls of cerebral arteries and impair the perivascular drainage of solutes from the brain. Mice were immunized against ovalbumin and then challenged by intracerebral microinjection of ovalbumin. Perivascular drainage of solutes was quantified following intracerebral microinjection of soluble fluorescent 3kDa dextran into the brain at different time intervals after intracerebral challenge with ovalbumin.. Ovalbumin, IgG and complement C3 co-localized in basement membranes of artery walls 24 hrs after challenge with antigen; this was associated with significantly reduced drainage of dextran in immunized mice.. Perivascular drainage along artery walls returned to normal by 7 days. These results indicate that immune complexes form in association with basement membranes of cerebral arteries and interfere transiently with perivascular drainage of solutes from the brain. Immune complexes formed during immunotherapy for AD may similarly impair perivascular drainage of soluble Aβ and increase severity of CAA.

Topics: Alzheimer Disease; Animals; Antigen-Antibody Complex; Basement Membrane; Brain; Cerebral Arteries; Complement C3; Dextrans; Immunoglobulin G; Immunotherapy; Mice, Inbred BALB C; Neuroimmunomodulation; Ovalbumin; Time Factors; Vaccination

Despite the existing knowledge regarding the neuropathology of Alzheimer's disease (AD), the cause of sporadic forms of the disease is unknown. It has been suggested that systemic inflammation may have a role, but the exact mechanisms through which inflammatory processes influence the pathogenesis and progress of AD are not obvious. Allergy is a chronic inflammatory disease affecting more than 20% of the Western population, but the effects of allergic conditions on brain functions are largely unknown. The aim of this study was to investigate whether or not chronic peripheral inflammation associated with allergy affects the expression of AD-related proteins and inflammatory markers in the brain. On the basis of previously described models for allergy in mice we developed a model of chronic airway allergy in mouse, with ovalbumin as allergen. The validity of the chronic allergy model was confirmed by a consistent and reproducible eosinophilia in the bronchoalveolar lavage (BAL) fluid of allergic animals. Allergic mice were shown to have increased brain levels of both immunoglobulin (Ig) G and IgE with a widespread distribution. Allergy was also found to increase phosphorylation of tau protein in the brain. The present data support the notion that allergy-dependent chronic peripheral inflammation modifies the brain inflammatory status, and influences phosphorylation of an AD-related protein, indicating that allergy may be yet another factor to be considered for the development and/or progression of neurodegenerative diseases such as AD.

Topics: Allergens; Alzheimer Disease; Animals; Brain; Bronchoalveolar Lavage Fluid; Chronic Disease; Disease Models, Animal; Eosinophilia; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Inflammation; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Phosphorylation; tau Proteins

Aβ(1-40) coated 20 nm gold colloidal nanoparticles exhibit a reversible color change as pH is externally altered between pH 4 and 10. This reversible process may contain important information on the initial reversible step reported for the fibrillogenesis of Aβ (a hallmark of Alzheimer's disease). We examined this reversible color change by microscopic investigations. AFM images on graphite surfaces revealed the morphology of Aβ aggregates with gold colloids. TEM images clearly demonstrate the correspondence between spectroscopic features and conformational changes of the gold colloid.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Gold Colloid; Metal Nanoparticles; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Ovalbumin; Peptide Fragments; Protein Conformation; Proteins; Water

Abnormal protein processing and modification is associated with Alzheimer's disease (AD) pathology. The role of phosphorylation in AD has been studied extensively because the presumed abnormal phosphorylation of tau protein is believed to play a role in the formation of paired helical filaments. Glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues is a dynamic protein modification of intracellular proteins, and it shares similar features with protein phosphorylation. In this study, O-GlcNAc glycosylation of proteins from autopsied human brains with confirmed AD and non-AD age-matched controls was examined. O-GlcNAcylation was demonstrated by labeling protein extracts with [3H]galactose in the presence of galactosyltransferase and subsequent analyses of saccharide-protein linkage and saccharide structure. The number of O-GlcNAc-containing proteins and the overall O-GlcNAc level do not appear to be different between AD and control brain tissues. The only significant change observed is a marked reduction of O-GlcNAcylated clathrin assembly protein-3 (AP-3) in AD. The reduction is more evident in brain neocortical regions, and there appears to be a negative correlation between O-glycosylated AP-3 and the density of neurofibrillary tangles. These data suggest a possible association between the O-glycosylated AP-3 and AD pathology.

Topics: Acetylation; Acetylglucosamine; Adaptor Proteins, Vesicular Transport; Aged; Aged, 80 and over; Alzheimer Disease; Cerebellum; Enzyme Inhibitors; Female; Frontal Lobe; Galactose; Galactosyltransferases; Humans; Male; Middle Aged; Molecular Weight; Monomeric Clathrin Assembly Proteins; Nerve Tissue Proteins; Neurofibrillary Tangles; Oligosaccharides; Ovalbumin; Phosphoproteins; Phosphorylation; Tritium