A5040780499- Glioma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Brain Metastases and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Amino Acid Enzymes and Metabolism
- Ion channel regulation and function
- Meningioma and schwannoma management
- Cancer Genomics and Diagnostics
- Vascular Malformations Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Receptor Mechanisms and Signaling
- Prion Diseases and Protein Misfolding
- Hedgehog Signaling Pathway Studies
- Neurogenesis and neuroplasticity mechanisms
- RNA modifications and cancer
- Retinal Development and Disorders
- Neurofibromatosis and Schwannoma Cases
- Nicotinic Acetylcholine Receptors Study
- Pain Mechanisms and Treatments
Ludwig-Maximilians-Universität München
2015-2024
Karl Landsteiner University of Health Sciences
2023-2024
German Center for Neurodegenerative Diseases
2012-2024
German Cancer Research Center
2016-2023
LMU Klinikum
2017-2023
Deutschen Konsortium für Translationale Krebsforschung
2020-2023
Heidelberg University
2016
Charité - Universitätsmedizin Berlin
2016
University Hospital Heidelberg
2016
Otto-von-Guericke University Magdeburg
2016
Uptake through the dopamine transporter (DAT) represents primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that (DA) taken up by replenish synaptic vesicle stores for subsequent release, molecular details of this are not completely understood. Here, we identified protein synaptogyrin-3 as a DAT interacting using split ubiquitin system. This interaction was confirmed coimmunoprecipitation experiments heterologous cell lines and mouse colocalized...
Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a promising drug target for the treatment of Alzheimer's disease. Prolonged BACE1 inhibition interferes with structural and functional synaptic plasticity in mice, most likely by altering metabolism substrates. Seizure 6 (SEZ6) predominantly cleaved BACE1, Sez6 knockout mice share some phenotypes inhibitor-treated mice. We investigated whether SEZ6 involved inhibition-induced alterations.The function NB-360, novel blood-brain...
Many membrane proteins incur a folding problem during biosynthesis; only fraction thereof is exported from the endoplasmic reticulum (ER), because quality control stringent. This also true for G protein-coupled receptors. Here, we identify deubiquitinating enzyme Usp4 as an interaction partner of A2a adenosine receptor, Gs-coupled receptor. binds to carboxyl terminus A2A receptor and allows its accumulation deubiquinated protein. relaxes ER enhances cell surface expression functionally...
Imaging of optical reporters neural activity across large populations neurones is a widely used approach for investigating the function circuits in slices and vivo. Major challenges analysing such experiments include automatic identification synapses, extraction dynamic signals, assessing temporal spatial relationships between active units relation to gross structure circuit. We have developed an integrated set software tools, named SARFIA, by which these aspects imaging can be analysed...
Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer's disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics these processes. In particular, question as whether synapse precedes or follows formation remains unanswered. To address this question, and learn more underlying kinetics, we simultaneously imaged amyloid by applying two-photon vivo microscopy through cranial window double...
The kinetics of amyloid plaque formation and growth as one the characteristic hallmarks Alzheimer's disease (AD) are fundamental issues in AD research. Especially question how fast plaques grow to their final size after they born remains controversial. By long-term two-photon vivo imaging we monitored individual methoxy-X04-stained over 6 weeks 12 18 months old Tg2576 mice. We found that mice, newly appearing were initially small volume subsequently grew time. rate was inversely proportional...
Central nervous glycogen synthase kinase 3β (GSK3β) is implicated in a number of neuropsychiatric diseases, such as bipolar disorder, depression, schizophrenia, fragile X syndrome or anxiety disorder. Many drugs employed to treat these conditions inhibit GSK3β either directly indirectly. We studied how conditional knockout affected structural synaptic plasticity. Deletion the gene subset cortical and hippocampal neurons adult mice led reduced spine density. In vivo imaging revealed that this...
BACE1 is the rate-limiting protease in production of synaptotoxic β-amyloid (Aβ) species and hence one prime drug targets for potential therapy Alzheimer's disease (AD). However, so far pharmacological inhibition failed to rescue cognitive decline mild-to-moderate AD patients, which indicates that treatment at symptomatic stage might be too late. In current study, chronic vivo two-photon microscopy was performed a transgenic model monitor impact on early pathology. The longitudinal approach...
To successfully treat Alzheimer's disease (AD), pathophysiological events in preclinical stages need to be identified. Preclinical AD refers the that exhibit amyloid deposition brain but have normal cognitive function, which are replicated young adult APPswe/PS1deltaE9 (deltaE9) mice. By long-term vivo two-photon microscopy, we demonstrate impaired adaptive spine plasticity these transgenic mice illustrated by their failure increase dendritic density and form novel neural connections when...
Background An integrated diagnosis consisting of histology and molecular markers is the basis current WHO classification system gliomas. In patients with suspected newly diagnosed or recurrent glioma, stereotactic biopsy an alternative in cases which microsurgical resection deemed to not be safely feasible indicated. this retrospective study, we aimed analyze both diagnostic yield safety a standardized technique. Material Methods The institutional database was screened for frame-based...
Abstract Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class “spinal ependymoma” (SP-EPN) represent most common intramedullary neoplasms in children adults. However, their developmental origin is ill-defined, data are scarce, potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events loss chromosome 22q NF2 mutations, but neither frequency these alterations nor...
Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression largely restricted to brain. It thought play role in delivery RNA dendrites polarized neurons. To investigate function Stau2 mature neurons, we interfered with by interference (RNAi). Mature neurons lacking displayed significant reduction number dendritic spines and an increase filopodia-like structures. The PSD95-positive synapses miniature excitatory postsynaptic currents were markedly...
A major neuropathological hallmark of Alzheimer's disease is the deposition amyloid plaques in brains affected individuals. Amyloid mainly consist fibrillar β-amyloid, which a cleavage product precursor protein. The amyloid-cascade-hypothesis postulates Aβ accumulation as central event initiating toxic cascade leading to pathology and, ultimately, loss cognitive function. We studied kinetics β-amyloid Tg2576 mice, overexpress human protein with Swedish mutation. Utilizing long-term...
Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that associated with extracellular depositions of amyloid β (Aβ) have been observed to contribute synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course this axonal pathology is high relevance comprehend progression disease over time. We performed a long-term vivo study (up 210 days two-photon imaging) two transgenic mouse models (dE9xGFP-M APP-PS1xGFP-M). Interestingly, AxDs were formed...
Alzheimer’s disease (AD) is thought to be caused by accumulation of amyloid-β protein (Aβ), which a cleavage product amyloid precursor (APP). Transgenic mice overexpressing APP have been used recapitulate pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) are extensively studied. express with Swedish mutation develop plaques late in their life, while cognitive deficits observed young age. In contrast, deltaE9 mutant presenilin-1 early but show typical old To unveil the reasons for...
Abstract Background Myxopapillary ependymoma (MPE) is a heterogeneous disease regarding histopathology and outcome. The underlying molecular biology poorly understood, markers that reliably predict the patients’ clinical course are unknown. Methods We assembled cohort of 185 tumors classified as MPE based on DNA methylation. Methylation patterns, copy number profiles, MGMT promoter methylation were analyzed for all tumors, 106 evaluated histomorphologically, RNA sequencing was performed 37...
Abstract Medulloblastomas (MBs) are malignant pediatric brain tumors that molecularly and clinically heterogenous. The application of omics technologies—mainly studying nucleic acids—has significantly improved MB classification stratification, but treatment options still unsatisfactory. proteome their N-glycans hold the potential to discover relevant phenotypes targetable pathways. We compile a harmonized dataset 167 MBs integrate findings with DNA methylome, transcriptome N-glycome data....
Like all members of the Na(+)/Cl(-)-dependent neurotransmitter transporter family, rat gamma-aminobutyric acid transporter-1 (GAT1) is sorted and targeted to specialized domains cell surface. Here we identify two discontinuous signals in carboxyl terminus GAT1 that cooperate drive surface expression. This conclusion based on following observations. Upon deletion last 37 amino acids, resulting GAT1-Delta37 remained trapped endoplasmic reticulum. The presence 10 additional residues...