A5101754501- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Connexins and lens biology
- Adenosine and Purinergic Signaling
- Cellular transport and secretion
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Protease and Inhibitor Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Proteoglycans and glycosaminoglycans research
- Nicotinic Acetylcholine Receptors Study
- Nuclear Receptors and Signaling
- Neuroscience of respiration and sleep
- Cholesterol and Lipid Metabolism
- Magnetic and Electromagnetic Effects
- Protein Kinase Regulation and GTPase Signaling
- 14-3-3 protein interactions
- Hearing, Cochlea, Tinnitus, Genetics
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- GDF15 and Related Biomarkers
- Click Chemistry and Applications
- Microtubule and mitosis dynamics
- Algal biology and biofuel production
- Neuroinflammation and Neurodegeneration Mechanisms
Sistema (Russia)
2020
Institute of Cell Biophysics
2019
German Center for Neurodegenerative Diseases
2013-2014
Medizinische Hochschule Hannover
2013-2014
Helmholtz Association of German Research Centres
2013
Heidelberg University
2003-2012
University Hospital Heidelberg
2003-2012
Max Planck Institute for Brain Research
2007
It is well established that the proteolytic processing of β-amyloid precursor protein (APP) generates (Aβ), which plays a central role in pathogenesis Alzheimer's disease (AD). In contrast, physiological APP and its numerous fragments question whether loss these functions contributes to AD are still unknown. To address this question, we replaced endogenous locus by gene-targeted alleles generated two lines knock-in mice exclusively express deletion variants corresponding either secreted...
Extracellular ATP controls various signaling systems including propagation of intercellular Ca 2+ signals (ICS). Connexin hemichannels, P2x7 receptors (P2x7Rs), pannexin channels, anion vesicles, and transporters are putative conduits for release, but their involvement in ICS remains controversial. We investigated cochlear organotypic cultures, which acts as an IP 3 -generating agonist evokes responses that have been linked to noise-induced hearing loss development hair cell-afferent...
The function of P2X(7) receptors (ATP-gated ion channels) in innate immune cells is unclear. In the setting Toll-like receptor (TLR) stimulation, secondary activation channels has been linked to pro-caspase-1 cleavage and cell death. Here we show that death a surprisingly early triggered event. We using live-cell imaging transient (1-4 min) stimulation mouse macrophages with high extracellular ATP ([ATP]e) triggers delayed (hours) death, indexed as DEVDase (caspase-3 caspase-7) activity....
Presenilins (PSs) are components of the gamma-secretase complex that mediates intramembranous cleavage type I membrane proteins. We show is involved in regulation cellular lipoprotein uptake. Loss function decreased endocytosis low-density (LDL) receptor. The uptake lipoproteins led to upregulation cholesterol biosynthesis by increased expression CYP51 and enhanced metabolism lanosterol. Genetic deletion PS1 or transgenic mutants cause early-onset Alzheimer's disease accumulation substrates...
Cdc42 (cell division cycle 42) is a member of the Rho GTPase family which regulates variety cellular activities by controlling actin cytoskeleton and gene expression. expressed in form two splice variants. The canonical isoform prenylated (Cdc42-prenyl), whereas brainspecific can be palmitoylated (Cdc42-palm). In present study we have demonstrated palmitoylation endogenous rodent human brains identified Cys(188) Cys(189) as acylation sites Cdc42-palm. Moreover, shown that also prenylated....
Abstract Background The β-amyloid precursor protein (APP) and the related precursor-like proteins (APLPs) undergo complex proteolytic processing giving rise to several fragments. Whereas it is well established that Aβ accumulation a central trigger for Alzheimer's disease, physiological role of APP family members their diverse products still largely unknown. secreted APPsα ectodomain has been shown be involved in neuroprotection synaptic plasticity. γ-secretase-generated intracellular domain...
ClC-3 is a member of the CLC family anion channels and transporters that localizes to early late endosomes as well synaptic vesicles (SV). Its genetic disruption in mouse models results pronounced hippocampal retinal neurodegeneration, suggesting might be important for normal excitatory and/or inhibitory neurotransmission central neurons. To characterize role glutamate accumulation SV we compared glutamatergic transmission cultured neurons from WT Clcn3-/- mice. In amplitude frequency...
Lutein is a widespread carotenoid in the world, which characterized by remarkable antioxidant activity. The impact of lutein for treatment chronic inflammation disorders makes it an important supplement support active human longevity. can inhibit proinflammatory NF-kappaB pathway, Nox-enzyme and VEGF-related pathologies. Despite lack provitamin activity, often denoted as “the eye vitamin”. main aim this mini-review analysis possible mechanisms effects focusing on their superior...
Abstract A variety of connexins are expressed in the diverse cell types central nervous system and thought to regulate some functional properties exhibited by immature mature cells. proper understanding role specific these processes requires an unambiguous characterization their spatial temporal pattern expression. In order define cellular distribution connexin 26 (Cx26) mouse we have generated a reporter allele ( Cx26 lacZ ) genetically manipulating locus so that β‐galactosidase gene is...
Abstract Proteolytical cleavage of the β‐amyloid precursor protein (APP) generates β‐amyloid, which is deposited in brains patients suffering from Alzheimer's disease (AD). Despite well‐established key role APP for AD pathogenesis, physiological function and its close homologues APLP1 APLP2 remains poorly understood. Previously, we generated –/– mice that proved viable, whereas triple knockouts died shortly after birth, likely due to deficits neuromuscular synaptic transmission. Here,...
Within the frames of Alfvén sweep maser theory description morphological features geomagnetic pulsations in ionosphere with frequencies (0.1-10 Hz) vicinity Schumann resonance (7.83 is obtained. It shown that related regular spectral shapes determined by "viscosity" and "elasticity" magneto-plasma medium control nonlinear relaxation energy deviation wave around its equilibrium value. Due to fact frequency bands resonant structures practically coincide band delta- partially theta-rhythms...
Identification of individuals at risk for developing Alzheimer's disease (AD) is an important issue its pretreatment. Perspective studies predicting the are based on genetic approaches emerging from nucleotide polymorphism analysis in different loci through entire genome AD patients. Considerable diversity genes located these regions raise question this diversity's peculiar role development. The mechanisms have been shown to be associated with gene variation, increased beta-amyloid...
The role of APP as the precursor Aβ peptide accumulating in Alzheimer's disease is well established. By contrast, its physiological function and question whether a loss these functions contributes to pathogenesis remains largely unresolved. member gene family including APP–like proteins APLP1 APLP2. We previously demonstrated that single mutants are viable exhibiting only minor phenotype, whereas APLP2–/–APLP1–/–– APLP2–/–APP–/––mice proved lethal postnatally. Triple knockout mice survive...
It is well established that the proteolytic processing of amyloid precursor protein (APP) plays a central role in pathogenesis Alzheimers disease (AD). In contrast, physiological APP and its numerous fragments question whether loss these functions contributes to AD are still unknown. To address this question, we previously generated two lines knockin (KI) mice express deletion variants corresponding either secreted ectodomain (APPsalpha-KI) or C-terminal truncation lacking YENPTY interaction...