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Article
Open AccessiRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I
Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this context, in t...
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Article
Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging
Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic pro...
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Article
Open AccessA microglial activity state biomarker panel differentiates FTD-granulin and Alzheimer’s disease patients from controls
With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.
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Article
Open AccessReactivated endogenous retroviruses promote protein aggregate spreading
Prion-like spreading of protein misfolding is a characteristic of neurodegenerative diseases, but the exact mechanisms of intercellular protein aggregate dissemination remain unresolved. Evidence accumulates t...
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Article
Open AccessTargeting the TCA cycle can ameliorate widespread axonal energy deficiency in neuroinflammatory lesions
Inflammation in the central nervous system can impair the function of neuronal mitochondria and contributes to axon degeneration in the common neuroinflammatory disease multiple sclerosis (MS). Here we combine...
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Article
Open AccessThe Alzheimer’s disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130
The protease BACE1 is a major drug target for Alzheimer’s disease, but chronic BACE1 inhibition is associated with non-progressive cognitive worsening that may be caused by modulation of unknown physiological ...
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Article
Open AccessHelical stability of the GnTV transmembrane domain impacts on SPPL3 dependent cleavage
Signal-Peptide Peptidase Like-3 (SPPL3) is an intramembrane cleaving aspartyl protease that causes secretion of extracellular domains from type-II transmembrane proteins. Numerous Golgi-localized glycosidases ...
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Article
Open AccessExperimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae
Brain Aβ deposition is a key early event in the pathogenesis of Alzheimer´s disease (AD), but the long presymptomatic phase and poor correlation between Aβ deposition and clinical symptoms remain puzzling. To ...
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Article
Open AccessThe β-Secretase Substrate Seizure 6–Like Protein (SEZ6L) Controls Motor Functions in Mice
The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ...
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Article
Open AccessProteomic profiling in cerebral amyloid angiopathy reveals an overlap with CADASIL highlighting accumulation of HTRA1 and its substrates
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 t...
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Article
Open AccessHighly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic ...
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Article
Open AccessLoss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia
Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in NPC1, resulting in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is a prominent pathological...
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Article
Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity
Mitochondria vary in morphology and function in different tissues; however, little is known about their molecular diversity among cell types. Here we engineered MitoTag mice, which express a Cre recombinase-depen...
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Article
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer’s disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of f...
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Article
Open AccessIncreased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor
The tissue inhibitor of metalloproteinases-3 (TIMP-3) is a major regulator of extracellular matrix turnover and protein shedding by inhibiting different classes of metalloproteinases, including disintegrin met...
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Article
CADASIL brain vessels show a HTRA1 loss-of-function profile
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and a phenotypically similar recessive condition (CARASIL) have emerged as important genetic model diseases ...
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Article
Proteasen in der Alzheimer-Forschung – Freund oder Feind?
Proteases have a central role in Alzheimer’s disease, but their use as drug targets is difficult as they have a broad substrate spectrum. Using the example of the Alzheimer α- and β-secretase, this article dem...
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Article
Open AccessSeizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons
The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer’s disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the...
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Article
Open AccessQuantitative proteomics reveals altered expression of extracellular matrix related proteins of human primary dermal fibroblasts in response to sulfated hyaluronan and collagen applied as artificial extracellular matrix
Fibroblasts are the main matrix producing cells of the dermis and are also strongly regulated by their matrix environment which can be used to improve and guide skin wound healing processes. Here, we systemati...
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Article
Open AccessOptimization of parameters for coverage of low molecular weight proteins
Proteins with molecular weights of <25 kDa are involved in major biological processes such as ribosome formation, stress adaption (e.g., temperature reduction) and cell cycle control. Despite their importance,...
