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Results for “Protein Aggregates”

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At least 19 recordsLinked to original sources
PubMed2025

Prediction and Evaluation of Protein Aggregation with Computational Methods.

Protein and peptide aggregation has recently become one of the most studied biomedical problems due to its central role in several neurodegenerative disorders and of biotechnological importance. Multiple in silico methods, databases, tools, and algorithms have been developed to predict aggregation of proteins and peptides to better understand fundamental mechanisms of various aggregation diseases. Here, we attempt to provide a brief overview of bioinformatic methods and tools to better understand molecular mechanisms of aggregation disorders. Furthermore, through a better understanding of protein aggregation mechanisms, it might be possible to design novel therapeutic agents to treat and hopefully prevent protein aggregation diseases.

Computational Biology↗
PubMed1979

Anaphylactoid reactions to infusions of plasma protein and human serum albumin. Role of aggregated proteins and of stabilizers added during production.

Six patients suffering from anaphylactoid reactions after infusion of pasteurized plasma (PP) or human serum albumin (HSA) were investigated. Clinical symptoms ranged from urticaria and hypotension to cardiac arrest. Immunoglobulin levels, especially of IgA, were normal, as were concentrations of complement factors C3, C4 and factor B. In skin and lymphocyte transformation tests patients, with the exception of one severely allergic to protein, did not react to the monomeric pure HSA. Five out of six patients reacted against HSA aggregates and three patients to the HSA modified by caprylate added as stabilizer during commercial HSA production. It is concluded that the anaphylactoid reactions developing after PP or HSA infusion result from a non-specific reaction to protein aggregates and in some cases possibly from a specific immune response to the caprylate-modified HSA.

Anaphylaxis↗
PubMed2026

Colorimetric gold nanosensors for monitoring protein aggregation: implications for Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It remains a major public health challenge due to the lack of early diagnostic tools and effective disease-modifying therapies. Molecularly, AD is characterized by extracellular amyloid-β (Aβ) plaques and intracellular Tau tangles, as well as soluble oligomers that are likely the neurotoxic species. However, the transient and heterogeneous nature of these oligomers makes them difficult to detect using conventional biosensing approaches. Nanomaterial-based colorimetric biosensors have emerged as promising platforms for detecting protein aggregates and discovering aggregation inhibitors. Specifically, the localized surface plasmon resonance properties of metallic nanomaterials can enable rapid, label-free, and visually detectable colorimetric sensing of molecular interactions. These features can be leveraged to monitor protein aggregation processes in real time and achieve high-throughput screening of aggregation inhibitors, which may collectively enable early detection and timely intervention of AD progression. This Review Article presents the design and engineering of gold-nanomaterial-based colorimetric biosensors for monitoring protein aggregation and highlights the current challenges and emerging opportunities for applying these nanosensors to combat AD.

Journal Article↗
PubMed1978

Cross-linking of lipid bilayers by central nervous system myelin basic protein: aggregation of free and vesicle-bound protein.

Central nervous system myelin basic protein binds to the zwitterionic lipid, egg diacylphosphatidylcholine, over a wide range of pH and ionic strength. Lipid vesicles containing the protein have been observed to increase in size and to aggregate. The size increase is most marked at very low ionic strengths whereas aggregation is evident at ionic strengths from 0.001 to 0.35. The pH and ionic-strength dependence of this aggregation closely follows that of the self-association of the protein, suggesting that vesicle association is mediated by binding between polypeptides attached to different vesicles. Basic protein is monomeric at low pH but above pH 6 self-associates yielding primarily small oligomers (probably dimers) and minor amounts of higher species. It is envisaged that each protein molecule possesses two distinct binding sites, one capable of association with lipid bilayers and the second with another protein molecule. Basic protein is found predominantly on the intracellular surface of the myelin membrane. Given the ability of the protein to act as a bridge between lipid bilayer vesicles in vitro it is proposed that it may perform a similar function in vivo, serving to cross-link the inner surfaces of the oligodendroglial cell membrane. This protein function could lead to formation of the long cellular processes which encircle the nerve cell axon and could assist in stabilizing the highly ordered myelin structure which results.

Animals↗
PubMed1979

An extrinsic membrane polypeptide associated with high-molecular-weight protein aggregates in human cataract.

A 43,000-dalton polypeptide has been isolated from the high-molecular-weight disulfide-rich fraction of the water-insoluble protein of human cataractous lenses. On the basis of immunochemical reactivity and fluorescent antibody binding, this polypeptide is localized in the membrane region of the lens cell. This observation suggests an interaction between the soluble lens proteins and membrane-associated polypeptides in the formation of large protein aggregates which may cause cataract.

Antibody Specificity↗
PubMed2025

Benchmark for Quantitative Global and Redox Proteomics Analysis by Combining Protein-Aggregation Capture and Data Independent Acquisition.

Oxidative damage plays a critical role in various diseases including cardiovascular and neurological disorders. Thiol redox reactions, acting as oxidative stress sensors, influence protein structure and function. Redox proteomics, based on the differential alkylation of cysteine sites followed by mass spectrometry, enables the comprehensive analysis of thiol redox status in cells and tissues. However, these approaches require extensive sample manipulation and are not compatible with data-independent acquisition techniques. Here, we introduce PACREDOX, an innovative strategy based on protein aggregation capture (PAC), and demonstrate its compatibility with library-free DIA. Compared with traditional methods such as FASILOX, PACREDOX reduces preparation time and costs while maintaining thiol and proteome coverage. To enable library-free DIA, we corrected in silico spectral libraries in DIA-NN using experimental retention time data from methylthiolated-Cys peptides. PACREDOX with DIA was benchmarked against FASILOX in a myocardial infarction model, yielding the same biological insights, while enhancing peptide and protein coverage. Our results underscore the potential and efficiency of this methodology for studying oxidative damage. Overall, PACREDOX offers an automatable, high-throughput, and cost-effective strategy for redox proteomics.

Proteomics↗
PubMed2026

Influence of protein aggregates, extracellular vesicles, and lipoprotein fusion on ionizable lipid nanoparticles protein corona analysis.

Since 2018, ionizable lipid nanoparticles (LNPs) have revolutionized nucleic acid therapeutics. However, achieving potent extrahepatic delivery remains a formidable challenge, primarily due to rapid hepatic uptake driven by apolipoprotein adsorption. While analyzing the LNP protein corona is essential for engineering organ-specific tropism, these soft materials present unique analytical hurdles. Co-isolation of blood-borne contaminants, such as extracellular vesicles and lipoproteins, often masks the true corona composition. This perspective examines the critical need for refined proteomic strategies to distinguish genuine corona proteins from impurities. We propose tailored investigative approaches, suggesting the LNP protein corona significantly differs from the rigid shells observed on inorganic nanoparticles.

Nanoparticles↗
PubMed1979

Further investigation of the role of calcium in human lens protein aggregation.

High-molecular-weight (HMW) protein from human cataractous lenses, isolated by differential centrifugation, was deaggregated in 7M urea and then reaggregated in either the presence or absence of 10 mM CaCl2. Over 90% of the material reaggregated in the presence of calcium appears to have a size greater than 50 X 10(6) daltons. By contrast, only 20% to 25% of the material reaggregated in the absence of calcium has molecular weight greater than 50 X 10(6) daltons. Disulfide formation during reaggregation is unlikely in the latter experiment, since the addition of 50 mM mercaptoethanol caused no change in results. About 60% to 70% of the low-molecular-weight (LMW) protein fraction deaggregated in 7M urea buffer can be converted to HMW species in the presence of 10 mM CaCl2, when the deaggregating agent is removed. However, only 5% to 10% of this protein is converted to HMW species if the deaggregation step is eliminated. Experiments with 45 Ca indicate that whereas calcium is necessary for the formation of the HMW aggregates, only one calcium per approximately 5 X 10(5) daltons remains bound in the reaggregated material. The data suggest that although calcium may be required to induce aggregation to HMW species, it is not required to stabilize such macromolecules. SDS-polyacrylamide gel electrophoresis of the HMW species formed upon reaggregation of the dissociated HMW species with calcium indicates the presence of all the major polypeptide subunits of the original HMW species present in the lens; however, reaggregation in the absence of calcium yields HMW species lacking in the 9600 dalton component.

Calcium Chloride↗
PubMed1975

The effect of manipulation of reticuloendothelial system activity on glomerular deposition of aggregated protein and immune complexes in two different strains of mice.

Glomerular uptake of intravenously administered aggregated albumen or immune complexes in mice appears to be inversely related to the activity of the reticuloendothelial system (RES). Stimulation of RES activity diminishes the amount of material appearing in the glomerulus whereas RES blockade enhances glomerular uptake. The possible relevance of these observations to experimental models of immune complex disease is discussed.

Anaphylaxis↗
PubMed1977

Anaphylactoid reactions due to non-immune complex serum protein aggregates.

The infusion of aggregate-containing i.v. human gamma-globulin as well as human serum albumin can lead to severe anaphylactoid reactions with decrease in mean arterial pressure, increase in pulmonary artery pressure and decrease in cardiac output in unsensitized dogs, while the deaggregated solutions are well tolerated. During these anaphylactoid reactions, no significant changes in the serum complement activity of the dogs were observed. In clinical human serum albumin incompatibility, stimulation with albumin aggregates led to a high response in the lymphocyte culture, whereas deaggregated albumin had no stimulatory effect. By deaggregation of horse anti-human lymphocyte globulin prior to clinical administration, the compatibility of ALG therapy was improved.

Anaphylaxis↗