A5038699828- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- COVID-19 Clinical Research Studies
- Advanced Neuroimaging Techniques and Applications
- CRISPR and Genetic Engineering
- Zebrafish Biomedical Research Applications
- Cholinesterase and Neurodegenerative Diseases
- Long-Term Effects of COVID-19
- Cellular Mechanics and Interactions
- Mitochondrial Function and Pathology
- Animal Genetics and Reproduction
- Prion Diseases and Protein Misfolding
- Ion Channels and Receptors
- Bacillus and Francisella bacterial research
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Retinopathy of Prematurity Studies
- Poxvirus research and outbreaks
- Dermatological and COVID-19 studies
- Hereditary Neurological Disorders
Universität Hamburg
2013-2024
University Medical Center Hamburg-Eppendorf
2012-2024
Max Planck Unit for Structural Molecular Biology
2002-2010
Max Planck Society
1993-2008
National Institutes of Health
1998-1999
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1998-1999
German Cancer Research Center
1992-1993
Max Planck Institute for Developmental Biology
1993
Heidelberg University
1992
We studied the effect of microtubule-associated tau protein on trafficking vesicles and organelles in primary cortical neurons, retinal ganglion cells, neuroblastoma cells. Tau inhibits kinesin-dependent transport peroxisomes, neurofilaments, Golgi-derived into neurites. Loss peroxisomes makes cells vulnerable to oxidative stress leads degeneration. In particular, amyloid precursor (APP) axons dendrites, causing its accumulation cell body. APP tagged with yellow fluorescent transfected by...
Aggregation of amyloid-beta (Abeta) and Tau protein are hallmarks Alzheimer's disease (AD), according to the Abeta-cascade hypothesis, Abeta is considered toxic for neurons a downstream target Abeta. We have investigated differentiated primary hippocampal early localized changes following exposure oligomers. Initial events become evident by missorting endogenous into somatodendritic compartment, in contrast axonal sorting normal neurons. In missorted dendritic regions there depletion spines...
Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected patients' brain tissues, its entry routes and resulting consequences not well understood. Here, we show a pronounced upregulation of interferon signaling pathways the neurovascular unit fatal By investigating susceptibility human induced pluripotent stem cell (hiPSC)-derived capillary endothelial-like cells (BCECs) to infection, found that BCECs were infected recapitulated transcriptional changes vivo....
Early hallmarks of Alzheimer's disease include the loss synapses, which precedes neurons and pathological phosphorylation aggregation tau protein. Mitochondrial dysfunction has been suggested as a reason, but evidence on role was lacking. Here, we show that transfection in mature hippocampal leads to an improper distribution into somatodendritic compartment with concomitant degeneration seen by disappearance spines presynaptic postsynaptic markers. This is accompanied transport inhibition...
Microtubule-dependent transport of vesicles and organelles appears saltatory because particles switch between periods rest, random Brownian motion, active transport. The can be regulated through motor proteins, cargo adaptors, or microtubule tracks. We report here a mechanism whereby associated proteins (MAPs) represent obstacles to motors which by affinity regulating kinase (MARK)/Par-1, family kinases that is known for its involvement in establishing cell polarity phosphorylating tau...
Long-haul transport along microtubules is crucial for neuronal polarity, and defects cause neurodegeneration. Tau protein stabilizes microtubule tracks, but in Alzheimer's disease it aggregates becomes missorted into the somatodendritic compartment. can inhibit axonal by obstructing motors on microtubules, yet tau itself still move axons. We therefore investigated movement live-cell fluorescence microscopy, FRAP (fluorescence recovery after photobleaching), FSM speckle microscopy). highly...
The kinesin KIF21B is implicated in several human neurological disorders, including delayed cognitive development, yet it remains unclear how dysfunction may contribute to pathology. One limitation that relatively little known about KIF21B-mediated physiological functions. Here, we generated Kif21b knockout mice and used cellular assays investigate the relevance of neuronal vivo function. We show a processive motor protein identify an additional role for regulating microtubule dynamics. In...
Yeast artificial chromosomes (YACs) represent the latest generation of vectors which have great advantage large insert size. The introduction YACs into mammalian cells and organisms has become an important goal, since it offers potential to study control complex transcription units identify genes by complementation. Microinjection nucleus is most direct efficient way delivering YAC DNA cells, but requires purification from remaining yeast chromosomes. Here we describe a detailed method for...
Mutations in the gene encoding microtubule-severing protein spastin (spastic paraplegia 4 [SPG4]) cause hereditary spastic (HSP), associated with neurodegeneration, spasticity, and motor impairment. Complicated forms (complicated HSP [cHSP]) further include cognitive deficits dementia; however, etiology dysfunctional mechanisms of cHSP have remained unknown. Here, we report specific working associative memory upon depletion mice. Loss spastin-mediated severing leads to reduced synapse...
Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, function, cognition, social behavior. However, the role of NBEA-mediated transport specific trafficking routes is unclear. Here, we highlight an additional function for local delivery surface re-insertion mouse neurons. dynamically interacts...
Journal Article Transgenic mice generated by pronuclear injection of a yeast artificial chromosome Get access Andreas Schedl, Schedl Institute Cell and Tumor Biology, German Cancer Research CenterW-6900 Heidelberg, Im Neuenheimer Feld 280, Germany Search for other works this author on: Oxford Academic PubMed Google Scholar Friedrich Beermann, Beermann + Present address: Swiss Experimental Research, Ch. des Boveresses, CH-1066 Epalinges, Switzerland Edda Thies, Thies Lluís Montoliu, Montoliu...
Amyloid-beta, a peptide derived from the precursor protein APP, accumulates in brain and contributes to neuropathology of Alzheimer's disease. Increased generation amyloid-beta might be caused by axonal transport inhibition, via increased dwell time APP vesicles thereby higher probability cleavage secretase enzymes residing on same vesicles. We tested this hypothesis using neuronal cell culture model inhibited imaging vesicular fluorescently tagged beta-secretase (BACE1)....
Kinesin superfamily proteins (KIFs) are molecular motors that transport cellular cargo along the microtubule cytoskeleton. KIF21B is a neuronal kinesin highly enriched in dendrites. The regulation and specificity of involves binding to individual adapters accessory proteins. Moreover, posttranslational modifications either motor protein, their cargos or tubulin regulate motility, recognition unloading cargos. Here we show ubiquitin E3 ligase TRIM3, also known as BERP, interacts with via its...
Abstract Many external signals influence growth cone motility, pathfinding, and the formation of synapses that lead to final map retinotectal system. Chick temporal retinal ganglion cell axons (RGCs) collapse retract after encountering posterior tectal cells in vitro . During this process lateral extensions appear along RGC axonal shaft. Lateral as nascent interstitial branches also defasciculating cones are trailing pioneer axon. branching controlled by repellent cues has recently been...
Abstract The recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV low CD4 T cell counts might develop a fulminant clinical mpox course increased mortality, secondary infections, necrotizing lesions. Fatal cases display high widespread MPXV tissue burden. underlying pathomechanisms are not fully understood. We report here the pathological findings an MPXV‐driven abscess gastrocnemius muscle requiring surgery...
Avian retinotectal and rodent retinocollicular systems are general model used to examine developmental processes that underpin topographically organized neuronal circuits. The two rely on guidance components establish their precise retinotopic maps, but many cellular events differ during development. For example, compared with the chick, a generally less restricted outgrowth pattern is observed when retinae innervate targets in rodents. Cellular or molecular distributions of may account for...
Abstract Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages cell division. The role p60 katanin in the mammalian brain with respect embryonic adult neurogenesis is poorly understood. Here, we generated Katna1 knockout mouse found that consistent critical mitosis, constitutive homozygous depletion lethal....
Abstract Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, decreased response to amphetamine. deficiency impairs social novelty detection while promoting the retention of spatial reference memory fear extinction recall. This...