Studies

Description

Proteolytic ectodomain shedding of membrane proteins is a fundamental mechanism to control the communication between cells and their environment. A key protease for membrane protein shedding is ADAM17, which requires a non-proteolytic subunit, either inactive Rhomboid 1 (iRhom1) or iRhom2 for its activity. While iRhom1 and iRhom2 are coexpressed in most tissues and appear to have largely redundant functions, the brain is an organ with predominant expression of iRhom1. Yet, little is ...

After demyelinating injury of the central nervous system, resolution of the mounting acute innate inflammation is crucial for the initiation of a regenerative response. To identify factors in lesion recovery after demyelination injury, we used a toxin-induced model, in which a single dose of lysolecithin is injected into the corpus callosum to induce a focal demyelinating lesion. Afterwards, we investigated the proteome of demyelinating lesions at different time points post injection (dpi) in a ...

Cerebral amyloid angiopathy (CAA) is an age-related condition and a major cause of intracerebral hemorrhage and cognitive decline that shows close links with Alzheimer's disease (AD). CAA is characterized by the aggregation of amyloid-β (Aβ) peptides and formation of Aβ deposits in the brain vasculature resulting in a disruption of the angioarchitecture. Capillaries are a critical site of Aβ pathology in CAA type 1 and become dysfunctional during disease progression. Here, applying an advanced ...

Here, we took advantage of well-defined mouse models for β-amyloidosis (APPPS1) to explore proteome changes in the cerebrospinal fluid which are related to these distinct proteopathic lesions. Non-targeted liquid chromatography-mass spectrometry revealed that the majority of proteins that undergo age- and disease-related changes in either mouse model was linked to microglia, and more specifically to previously described disease state-specific microglia transcriptomic signatures. The finding that ...

The earliest defining event in the pathogenesis of Alzheimer´s disease (AD) is the intracerebral deposition of Abeta, which starts at least 20 years before the onset of dementia. The link between Abeta and downstream neurodegeneration leading to dementia remains unclear, a critical gap in knowledge at a time when clinical trials are increasingly shifting to pre-symptomatic disease stages. Consequently, the design of preventive treatment strategies based on biomarkers remains an important challenge. ...

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of biological specimens imaged in 3D as a whole are lacking. Here, we present DISCO-MS, a technology combining whole-organ/ism imaging, deep learning-based image analysis, robotic tissue extraction and ultra-high sensitivity mass spectrometry. DISCO-MS yielded qualitative and quantitative proteomics data indistinguishable ...