Mass spectrometry is a powerful method to study protein complexes; however, biochemical reactions are typically beyond the scope of MS studies. Here, we have studied the gas-phase redox chemistry of the [copper(II) - amyloid β] complex and show that the sequence-dependence of this chemistry reflects key aspects of the known behaviour of different variants of the peptide.
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http://dx.doi.org/10.1039/d4an00693c | DOI Listing |
Alzheimers Dement
December 2024
Washington University School of Medicine, St. Louis, MO, USA.
Background: Alzheimer's disease neuropathology involves the deposition in brain of aggregates enriched with microtubule-binding-region (MTBR) of tau adopting an abnormal conformation between residues 306-378 in the core of aggregates. Anti-tau drugs targeting around this domain have the potential to interfere with the cell-to-cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235-250.
View Article and Find Full Text PDFBackground: Small, soluble oligomers, rather than mature fibrils, are the major neurotoxic agents in Alzheimer's disease (AD). In the last few years, Aprile and co-workers designed and purified a single-domain antibody (sdAb), called DesAb-O, with high specificity for Aβ oligomeric conformers. Recently, Cascella and co-workers showed that DesAb-O can selectively detect synthetic Aβ oligomers both in vitro and in cultured cells, neutralizing their associated neuronal dysfunction.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The goal of the TREAT-AD Center is to enable drug discovery by developing assays and providing tool compounds for novel and emerging targets. The role of microglia in neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Genome-wide association studies, whole genome sequencing, and gene-expression network analyses comparing normal to AD brain have identified risk and protective variants in genes essential to microglial function.
View Article and Find Full Text PDFBackground: Gut microbiota modulation of the brain function may present an opportunity to devise preventive or treatment strategies to manage impairments such as cognitive frailty (CF). This study aims to uncover the relationship between CF, gut microbiota, intestinal permeability and proteome.
Method: A total of 137 fecal samples of the elderly were collected, and subjected to DNA analysis, and enzyme-linked immunosorbent assays (ELISA).
Alzheimers Dement
December 2024
University of the Balearic Islands, Palma de Mallorca, Spain.
Background: Reactive astrocytes and neuron death by excitotoxicity are observed in Alzheimer's disease (AD). DHA-H (2-hydroxy-docosahexaenoic acid; 2-OH-C22:6 n-3) is a molecule under development that has demonstrated therapeutic efficacy in both cellular and 5xFAD mouse model of AD. DHA-H is metabolized through α-oxidation to yield HPA (Heneicosapentaenoic acid; C21:5 n-3).
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