Proteomics (Published)

Neurological diseases are on the rise – and as societies age, they affect an ever-increasing number of people, not only in Europe, but worldwide.

The Munich Cluster for Systems Neurology (SyNergy) investigates how complex neurological diseases such as Alzheimer's disease, stroke, and multiple sclerosis develop. Even though these diseases differ in their clinical manifestations, overlapping mechanisms are involved in their development. For example, the immune system gets activated in dementia, ...

This project serves as a centralized repository for omics datasets published by research groups within the SyNergy Cluster. It encompasses investigations such as proteomics and transcriptomics, which are further divided into individual studies led by SyNergy members. Each study is linked to relevant publications, assays and data files (with links to external repositories).

To explore investigations and their associated studies in more detail, please visit the 'Related items' tab on the Project ...

Anti-amyloid β-peptide (Aβ) immunotherapy was developed to reduce amyloid plaque pathology and slow cognitive decline during progression of Alzheimer's disease. Efficient amyloid clearance has been proven in clinical trials testing anti-Aβ antibodies, by their impact on cognitive endpoints correlating with the extent of amyloid removal. However, treatment is associated with adverse side effects, such as oedema and haemorrhages, which are potentially linked to the induced immune response. To improve ...

Despite numerous studies on fetal therapy for myelomeningoceles (MMC), the pathophysiology of this malformation remains poorly understood. This study aimed to analyze the biochemical profile and proteome of amniotic fluid (AF) supernatants from MMC fetuses to explore the prenatal pathophysiology. Biochemical analysis of 61 AF samples from MMC fetuses was compared with 45 healthy fetuses' samples. Proteome analysis was conducted in 18 MMC and 18 healthy singleton fetuses, and in 5 dichorionic ...

Advancing MS-based proteomics toward clinical applications evolves around developing standardized start-to-finish and fit-for-purpose workflows for clinical specimens. Steps along the method design involve the determination and optimization of several bioanalytical parameters such as selectivity, sensitivity, accuracy, and precision. In a joint effort, eight proteomics laboratories belonging to the MSCoreSys initiative including the CLINSPECT-M, MSTARS, DIASyM, and SMART-CARE consortia performed ...

The cell surface receptor TREM2 is a key genetic risk factor and drug target in Alzheimer's disease (AD). In the brain, TREM2 is expressed in microglia, where it undergoes proteolytic cleavage, linked to AD risk, but the responsible protease in microglia is still unknown. Another microglial-expressed AD risk factor is catalytically inactive rhomboid 2 (iRhom2, RHBDF2), which binds to and acts as a non-catalytic subunit of the metalloprotease ADAM17. A potential role in TREM2 proteolysis is not ...

The β-secretase β-site APP cleaving enzyme 1 (BACE1) is a major drug target for Alzheimer's disease (AD). Clinically tested BACE1 inhibitors induced unexpected cognitive side effects that may stem from their cross-inhibition of the homologous protease BACE2. Yet, little is known about BACE2 functions and substrates in vivo, and no biomarker is available to monitor the extent of BACE2 inhibition in vivo, particularly in cerebrospinal fluid (CSF). To identify a potential CSF biomarker for monitoring ...

Cells were collected and lysed in urea buffer (9 M Urea, 50 mM Tris pH 8, 150 mM NaCl, 1x Roche protease inhibitor cocktail) followed by short sonification. Samples were cleared by centrifugation and protein amounts were adapted. Protein reduction was performed with dithiothreitol (DTT; 5 mM final) for 25 min at 56°C and protein alkylation by the addition of iodoacetamide (14 mM final) for 30 min at room temperature. Protein mixtures were quenched with DTT and diluted 1:5 with 1 M Tris-Hcl, pH ...

Anti-amyloid β-peptide (Aβ) immunotherapy was developed as treatment for Alzheimer’s disease to reduce and prevent amyloid plaque pathology and its downstream consequences. Efficient amyloid plaque clearance has been proven in clinical trials with Aducanumab, Lecanemab and Donanemab. At least two of these antibodies slow memory decline to some extent and have beneficial effects on daily living activities. The therapeutic effects correlate with the efficacy of plaque removal. However, treatment ...

Despite numerous studies on fetal therapy for myelomeningoceles (MMC), the pathophysiology of this malformation remains poorly understood. This study aimed to analyze the biochemical profile and proteome of amniotic fluid (AF) supernatants from MMC fetuses to explore the prenatal pathophysiology. Proteome analysis was conducted in 18 MMC and 18 healthy singleton fetuses, as well as in 5 dichorionic pregnancies with MMC fetuses and their healthy co-twins. ELISA tests were used to validate proteome ...

Advancing MS-based proteomics towards clinical applications evolves around developing standardized start-to-finish and fit-for-purpose workflows for clinical specimens. Steps along the method design involve the determination and optimization of several bioanalytical parameters such as selectivity, sensitivity, accuracy, and precision. In a joint effort eight proteomics laboratories belonging to the MSCoreSys initiative including the CLINSPECT-M, MSTARS, DIASym, and SMART-CARE consortia performed ...

The cell surface receptor TREM2 is a key genetic risk factor and drug target in Alzheimer’s disease (AD). In the brain, TREM2 is expressed in microglia, where it undergoes proteolytic cleavage, linked to AD risk, but the responsible protease in microglia is unknown. Another microglia-expressed AD risk factor is inactive rhomboid 2 (iRhom2, RHBDF2), which acts as a non-catalytic subunit of the metalloprotease ADAM17. Its function in AD is unknown. To determine whether loss of iRhom2 and ADAM17 ...

The cell surface receptor TREM2 is a key genetic risk factor and drug target in Alzheimer’s disease (AD). In the brain, TREM2 is expressed in microglia, where it undergoes proteolytic cleavage, linked to AD risk, but the responsible protease in microglia is unknown. Another microglia-expressed AD risk factor is inactive rhomboid 2 (iRhom2, RHBDF2), which acts as a non-catalytic subunit of the metalloprotease ADAM17. Its function in AD is unknown. To determine whether loss of iRhom2 and ADAM17 ...