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9 Publications visible to you, out of a total of 9
An optimized quantitative proteomics method establishes the cell type-resolved mouse brain secretome.

Abstract (Expand)

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" (hiSPECS) method. 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 and brain function and to identify cell type-specific biomarkers for CNS diseases.

Authors: J. Tushaus, S. A. Muller, E. S. Kataka, J. Zaucha, L. Sebastian Monasor, M. Su, G. Guner, G. Jocher, S. Tahirovic, D. Frishman, M. Simons, S. F. Lichtenthaler

Date Published: 15th Oct 2020

Publication Type: Journal

Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis.

Abstract (Expand)

Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked … whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-kappaB-dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-alpha in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.

Authors: M. I. Cunha, M. Su, L. Cantuti-Castelvetri, S. A. Muller, M. Schifferer, M. Djannatian, I. Alexopoulos, F. van der Meer, A. Winkler, T. J. van Ham, B. Schmid, S. F. Lichtenthaler, C. Stadelmann, M. Simons

Date Published: 4th May 2020

Publication Type: Journal

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