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Delbridge, C.

Publications and source records attributed to Delbridge, C..

2 recordsLinked to original sources

A region-resolved proteomic map of the human brain enabled by high-throughput proteomics

Substantial efforts are underway that aim to deepen our understanding of human brain morphology, structure and function using high-resolution imaging as well has high-content molecular profiling technologies. The current work adds to these efforts by providing a comprehensive and quantitative protein expression map of 13 anatomically distinct brain regions covering more than 10,000 proteins. This was enabled by the optimization, characterization and implementation of a high-sensitivity and high-throughput micro-flow liquid chromatography timsTOF tandem mass spectrometry system (LC-MS/MS) capable of analyzing >2,000 consecutive samples prepared from formalin fixed paraffin embedded (FFPE) material. Analysis of this proteomic resource highlighted e.g. brain region-enriched protein expression patterns and functional protein classes, protein localization differences between brain regions and individual protein markers for specific brain regions. To facilitate access to and ease further mining of the data by the scientific community, all data can be explored online in a purpose-built Shiny App (https://brain-region-atlas.proteomics.ls.tum.de).

neuroscience↗

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the viruss acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spikes persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/535604v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b223eforg.highwire.dtl.DTLVardef@15539e9org.highwire.dtl.DTLVardef@4d17a9org.highwire.dtl.DTLVardef@14c63af_HPS_FORMAT_FIGEXP M_FIG C_FIG Short SummaryThe accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis presents potential molecular mechanisms and therapeutic targets for neurological complications in long-COVID-19 patients.

neuroscience↗