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Sponsored Artificial Intelligence: A Modern Approach, Global Edition Artificial Intelligence: A Modern Approach, Global Edition

Author

M. R. Larsen

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Open access Aug 2026

STEP-PTMs: Sequential TMT-based Enrichment and Profiling of Post-Translational Modifications

Application of STEP-PTM to TMT16-plex cerebral brain organoids enabled the quantification of 10,413 proteins, 2,969 metabolites, 19,655 phosphopeptides, 28,876 peptides containing reversibly modified cysteines, 9,723 peptides containing free cysteines, 1,716 intact sialylated N-linked glycopeptides and 771 lysine-acetylated peptides from the same biological samples.

Lucrezia Criscuolo, S. B. Elmkvist, Arkadiusz Nawrocki et al. · 0 citations
Jul 2026

Stimulus-Evoked Network Dynamics in Human Cortical Organoids: From a Graph-Computational Framework to Repeated-Stimulation Depression

A graph-computational framework to quantify stimulus-evoked propagation and revealed a control-validated phenomenon, that repeated stimulation reshapes organoid networks is established, but longitudinal designs in which every preparation is stimulated cannot separate this from developmental maturation.

E. Nadimi, V. C. Gogineni, Jan-Matthias Braun et al. · 0 citations
Jul 2026

Proteomic and Phosphoproteomic Characterization of Disease-Associated Alterations in Nerve Terminals and Protein Inclusions of Alzheimer's Disease Patients.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction, protein aggregation, and widespread molecular alterations in the brain. In this study, we applied quantitative mass spectrometry-based proteomics and phosphoproteomics to characterize synaptosomes and sarkosyl-insoluble protein inclusions from the post-mortem frontal lobes of AD and control cases. We identified >3700 proteins across both fractions, revealing AD-associated changes in synaptic composition and phosphorylation patterns. Proteomic analyses indicated mitochondrial deficits and disruptions in vesicle trafficking within synapses, whereas insoluble protein inclusions showed an accumulation of spliceosomal components and glial activation markers as well as an enrichment of N-terminally truncated amyloid beta peptides in AD cases, suggesting involvement of postfibrillar processing events mediated by specific proteases in amyloid plaque pathology. Phosphoproteomic analysis revealed extensive alterations in pathways regulating vesicle trafficking, Golgi homeostasis, and synaptic function. We observed increased tau phosphorylation at AD-associated sites in insoluble inclusions and distinct phosphorylation changes in synaptic tau, particularly at S285 and S305, suggesting altered tau function and aggregation properties. These findings provide new molecular insights into AD-related nerve terminal composition and protein aggregation, advancing our understanding of disease-associated changes at the subcellular level.

S. B. Elmkvist, Camilla Thygesen, Pia Jensen et al. · 0 citations

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