Alison M. Maxwell's research while affiliated with UCSF University of California, San Francisco and other places

... Of note, it has recently been shown that some differences are detected between AD and DS in the neuropathic spread of Aβ and Tau. 49) Experiments assessing the infectivity of Aβ and Tau prions to cultured cells demonstrated significant trends of increased Aβ and Tau prions in individuals with DS in an age-dependent manner, in contrast, the Aβ and Tau prions tend to decrease in individuals with AD who lived longer. 49) Cu has also been implicated in the pathogenesis of prion disease. ...

... Although amyloid structure seems to be stable across patients sharing the same pathology, it is also clear that amyloids are extremely sensitive to environmental conditions. For example, distinct strains formed by Aβ form at later stages of Down syndrome, suggesting that the convergence of ageing and disease-specific factors can dictate the formation of characteristic amyloid strains 163 . Cryo-EM studies of in vitro-prepared amyloid fibrils of tau and αS have shown that additives such as heparin or nucleic acids can substantially alter amyloid structure [164][165][166] , in a similar lateral mode of binding shown for amyloid-specific dyes 167 . ...

... While the pathological relevance of αS is generally established, its function remains elusive, although growing evidence points to a role in synaptic vesicles (SVs) trafficking (Auluck et al., 2010;Burre, 2015). A recursive feature in most of the putative functions of αS involves binding to biological membranes (Lorenzen et al., 2014;Snead and Eliezer, 2014;Fusco et al., 2018;Jacob et al., 2021), an interaction relevant to the normal form of αS in vivo (Newberry et al., 2020a;Newberry et al., 2020b) and influencing its aggregation (Perrin et al., 2001;Zhu and Fink, 2003;Breydo et al., 2012;Comellas et al., 2012;Galvagnion et al., 2015;Antonschmidt et al., 2021) and the toxicity of its oligomeric aggregates (Fusco et al., 2017). This interaction has been observed in different biological contexts, including the regulation of the homeostasis of SVs during neurotransmitter release (Wislet-Gendebien et al., 2006;Auluck et al., 2010), the localization to mitochondrial membranes or mitochondrial-associated membranes (Maltsev et al., 2013;Plotegher et al., 2014;Menges et al., 2017;Ordonez et al., 2018;Ramezani et al., 2019), where it has been proposed to mitigate the effects of oxidative stress, or the binding to lysosomal membranes (Bourdenx et al., 2014). ...

... The in silico alanine scanning of the H3 peptide-LAH31 mAb complex were also compared between crystal structure and docking models, showing the overall reproducibility of the docking calculation (Figs 4D and S8). While the accuracy of computational prediction remains a matter of debate, the approach utilized in this study represents a state-of-the-art method that is widely employed to address a range of protein design and biological problems [29][30][31][32][33]. The in silico alanine scanning of the H3 peptide-LAH31 complex highlighted the Glu103, Asn104, His106, and Leu110 as the determinants for the recognition of the H3 subtype by LAH31. ...

... Upon misfolding, Aβ acquires pathological properties, spreads throughout the brain and triggers a cascade of neurotoxic events, ultimately leading to neurodegeneration [8][9][10][11]. Remarkably, the size, the morphology and the localization of Aβ aggregates differ considerably in the brains of AD patients: this strengths the evidence that the disease is phenotypically heterogeneous, and such heterogeneity likely correlates with structural diversities of Aβ species [12][13][14][15][16][17]. Therefore, characterization of Aβ aggregates in the brain enables classification of AD in different subgroups [17]. ...

... Binding signal was detected for all six targets and significant enrichment was observed after multiple rounds of sorting ( Fig. S3 ). Deep sequencing of the final sorted populations revealed 1, 46,19,8,8, and 117 unique hits for HCY, WRF, ROC, APX, SN-38, and OHP, respectively. AF2 and Rosetta metrics for the identified hits revealed high confidence (pLDDTs ranging from 86.0 to 95.0), accuracy (Cα RMSDs less than 2.0 Å), and extensive molecular interactions (target median ddG < -30) and high shape complementarity (target median CMS > 240) to the ligand . ...