A5018755312- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Neurotransmitter Receptor Influence on Behavior
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Memory and Neural Mechanisms
- Cellular transport and secretion
- Attention Deficit Hyperactivity Disorder
- Neuroinflammation and Neurodegeneration Mechanisms
- Autism Spectrum Disorder Research
- Mitochondrial Function and Pathology
- Advanced Neuroimaging Techniques and Applications
- Nuclear Receptors and Signaling
- Computational Drug Discovery Methods
- Neurological disorders and treatments
- Cholinesterase and Neurodegenerative Diseases
- HER2/EGFR in Cancer Research
- Axon Guidance and Neuronal Signaling
- Carbohydrate Chemistry and Synthesis
- Botulinum Toxin and Related Neurological Disorders
- Estrogen and related hormone effects
- Peroxisome Proliferator-Activated Receptors
- Amyotrophic Lateral Sclerosis Research
QPS (Austria)
2013-2024
Bayer (Germany)
2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2006-2012
Salk Institute for Biological Studies
2012
National Institutes of Health
2006-2011
Institute of Neurobiology and Molecular Medicine
2009
Bielefeld University
2001-2007
Alzheimer's disease is characterized by accumulation of amyloid plaques and tau aggregates in several cortical brain regions. Tau phosphorylation causes formation neurofibrillary tangles neuropil threads. Phosphorylation at Ser202/Thr205 well since labeling this site used to assign Braak stage based on occurrence tangles. Only little known about the spatial temporal profile other phosphorylated (ptau) sites. Here, we investigate total ptau residues Tyr18, Ser199, Ser202/Thr205, Thr231,...
NRG1 and ERBB4 have emerged as some of the most reproducible schizophrenia risk genes. Moreover, Neuregulin (NRG)/ErbB4 signaling pathway has been implicated in dendritic spine morphogenesis, glutamatergic synaptic plasticity, neural network control. However, despite much attention this its effects on pyramidal cells received recently, presence ErbB4 these is still controversial. As knowledge precise locus receptor expression crucial to delineating mechanisms by which NRG elicits diverse...
Alterations in gamma-frequency oscillations are implicated psychiatric disorders, and polymorphisms NRG-1 ERBB4, genes encoding Neuregulin-1 (NRG-1) one of its receptors, designated ErbB4, associated with schizophrenia. Here we show that selectively increases the power kainate-induced, but not carbachol-induced, gamma acute hippocampal slices. NRG-1β is more effective than NRG-1α, a splice variant lower affinity for ErbB neither isoform affects network activity without prior induction...
Neuregulin-1 (NRG-1) is genetically linked with schizophrenia, a neurodevelopmental cognitive disorder characterized by imbalances in glutamatergic and dopaminergic function. NRG-1 regulates numerous processes and, the adult, suppresses or reverses long-term potentiation (LTP) at hippocampal synapses. Here we show that stimulates dopamine release hippocampus early-phase LTP via activation of D4 receptors (D4R). fails to depotentiate slices treated antipsychotic clozapine other more selective...
Neuregulins (NRGs) are ligands of ErbB receptor tyrosine kinases. The NRG1-ErbB4 pathway has been shown to modulate hippocampal synaptic plasticity and network oscillations in the adult rodent brain. To identify cells that mediate these effects, here we determine expression pattern ErbB4 four functionally distinct classes interneurons represent majority all inhibitory neurons hippocampus. On basis data from nine mice 25,000 cells, show is expressed positive for cholecystokinin (CCK, 54%),...
Synucleinopathies such as Parkinson's disease or multiple system atrophy are characterized by Lewy bodies in distinct brain areas. These aggregates mainly formed α-synuclein inclusions, a protein crucial for synaptic functions the healthy brain. Transgenic animal models of synucleinopathies frequently based on over-expression human wild type mutated under regulatory control different promoters. A promising model is Line 61 transgenic mouse that expresses transgene Thy-1 promoter. Here, we...
Abstract Background Progressive accumulation of α-synuclein (α-Syn) protein in different brain regions is a hallmark synucleinopathic diseases, such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy. α-Syn transgenic mouse models have been developed to investigate the effects on behavioral deficits neuropathology. However, onset progression pathology mice not fully characterized. For this purpose we investigated time course neuropathology PDGF-β human wild type...
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that associated with the aggregation of amyloid β protein (Aβ). Aβ oligomers are currently thought to be major neurotoxic agent responsible for development and progression. Thus, their elimination highly desirable therapy development. Our therapeutic approach aims at specific direct toxic by stabilizing monomers in an aggregation-incompetent conformation. We have proven our lead compound “D3”, all d-enantiomeric-peptide,...
Background The presence of gadolinium traces in the skin after administration gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs SFN rat foot pads by quantification intraepidermal nerve density (IENFD) multiple GBCA administrations and to evaluate concentration, chemical species, clearance. Materials Methods Fifty rats received eight intravenous injections either gadodiamide,...
Aggregation and misfolding of amyloid beta (Aβ) tau proteins, suggested to arise from post-translational modification processes, are thought be the main cause Alzheimer's disease (AD). Additionally, a plethora evidence exists that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), dyslipidemia pathogenesis AD. We thus investigated combinatory effect T2D human glutaminyl cyclase activity (pyroglutamylation), on pathology AD whether astaxanthin (ASX) treatment ameliorates...
Tauopathies, characterized by hyperphosphorylation and aggregation of tau protein, include frontotemporal dementias Alzheimer's disease. To explore disease mechanisms investigate potential treatments, we generated a transgenic (tg) mouse line overexpressing human tau441 with V337M R406W mutations. Biochemical characterization these TMHT (Thy-1 mutated tau) mice showed significant increase in transgene expression relative to endogenous murine Western blot multi-array immunosorbent assay. Only...
We demonstrated recently that frontal cortical expression of the Neuregulin (NRG) receptor ErbB4 is restricted to interneurons in rodents, macaques, and humans. However, little known about protein patterns other areas brain. In situ hybridization studies have shown high mRNA levels various subcortical areas, suggesting also expressed cell types than interneurons. Here, using highly-specific monoclonal antibodies, we provide first extensive report throughout cerebrum primates. show...
Neuregulin-1 (NRG-1) and its receptor ErbB4 are genetically associated with schizophrenia, a complex developmental disorder of high heritability but unknown etiology that has been proposed to result from deficits in functional connectivity synaptic plasticity. Based on pharmacological evidence, imbalances dopaminergic glutamatergic transmission systems believed contribute pathophysiology, genetic data supporting causative role for either sparse. Stimulation NRG-1/ErbB4 signaling inhibits or...
Senile plaques frequently contain Aβ-pE(3), a N-terminally truncated Aβ species that is more closely linked to AD compared other species. Tau protein highly phosphorylated at several residues in AD, and specifically phosphorylation Ser202/Thr205 known be increased AD. Several studies suggest formation of tau might each other. To evaluate if Aβ-pE(3) ptau levels correlate human transgenic mouse models, we analyzed cortical hippocampal brain tissue different Braak stages as well murine two...
Huntington’s disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result a devasting and lethal phenotype. Neurodegeneration HD begins striatum spreads other brain regions such as cortex hippocampus, causing motor cognitive dysfunctions. To understand signaling pathways involved HD, animal models mimic human pathology are used. The R6/2 mouse model was already shown present major caudate putamen regions, but recently...
In the present study, influence of postnatal environmental conditions on structural ontogeny orbital prefrontal cortex adult gerbils (Meriones unguiculatus) was examined. The animals were bred and reared either isolated in standard laboratory cages or grouped an object-filled environment. At age day 90, dopamine fibers stained immunocytochemically innervation density determined cortex. By comparison, restricted rearing produced a restraint subsequent maturation innervation, leading to fiber...
Gaucher disease is caused by a deficiency in glucocerebrosidase that can result non-neuronal as well neuronal symptoms. Common visceral symptoms are an increased organ size, specifically of the spleen, and glucosylceramide glucosylsphingosine substrate accumulations direct deficiency. Neuronal include motor deficits strong alterations cerebellum. To evaluate effect new compounds for treatment this devastating disease, animal models needed closely mimic human phenotype. The 4L/PS-NA mouse...