Biology subjects

Tüshaus, J.

Publications and source records attributed to Tüshaus, J..

2 recordsLinked to original sources

bioRxiv2023

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↗

bioRxiv2020

Quantitative secretome analysis establishes the cell type-resolved mouse brain secretome

To understand how cells communicate in the nervous system, it is essential to define their secretome, which is challenging for primary cells because of large cell numbers being required. Here, we miniaturized secretome analysis by developing the high-performance secretome-protein-enrichment-with-click-sugars method (hiSPECS). To demonstrate its broad utility, hiSPECS was used to identify the secretory response of brain slices upon LPS-induced neuroinflammation and to establish the cell type-resolved mouse brain secretome resource using primary astrocytes, microglia, neurons and oligodendrocytes. This resource allowed mapping the cellular origin of CSF proteins and revealed that an unexpectedly high number of secreted proteins in vitro and in vivo are proteolytically-cleaved membrane protein ectodomains. Two examples are neuronally secreted ADAM22 and CD200, which we identified as substrates of the Alzheimer-linked protease BACE1. hiSPECS and the brain secretome resource can be widely exploited to systematically study protein secretion, brain function and to identify cell type-specific biomarkers for CNS diseases.

neuroscience↗