A5072237751- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Hereditary Neurological Disorders
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Tryptophan and brain disorders
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Multiple Sclerosis Research Studies
- Nerve injury and regeneration
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- Hepatitis C virus research
- Metabolism and Genetic Disorders
Max Planck Institute for Multidisciplinary Sciences
2022-2025
Max Planck Institute of Experimental Medicine
2014-2025
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2018
Max Planck Society
1996-2015
ABSTRACT Like all other positive-strand RNA viruses, hepatitis C virus (HCV) induces rearrangements of intracellular membranes that are thought to serve as a scaffold for the assembly viral replicase machinery. The most prominent membranous structures present in HCV-infected cells double-membrane vesicles (DMVs). However, their composition and role HCV replication cycle poorly understood. To gain further insights into biochemcial properties HCV-induced membrane alterations, we generated...
The incidence of Alzheimer's disease (AD), the leading cause dementia, increases rapidly with age, but why age constitutes main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and structural integrity myelin sheaths1, latter which associated secondary neuroinflammation2,3. As support axonal energy metabolism neuronal health4-7, we hypothesized that loss could be an upstream for amyloid-β (Aβ) deposition, central neuropathological hallmark AD. Here identify...
Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant oligodendrocytes (OLs). By cell-type-specific deletion Bace1 a humanized knock-in AD model, APP
Abstract Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol rate-limiting for myelin biogenesis the developing CNS; however, whether cholesterol insufficiency MS, unclear. Here, we show relationship between cholesterol, myelination and neurological parameters mouse models of demyelination remyelination. In cuprizone model, acute disease reduces serum levels that can be restored by dietary...
Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral component essential rate limiting development CNS PNS myelin. Experiments with conditional mouse mutants lack cholesterol biosynthesis oligodendrocytes revealed minimal changes lipid composition are tolerated....
Abstract The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment cholesterol in the membrane. However, it unknown how concentrate above level found nonmyelin membranes. Here, we demonstrate critical role for proteolipids accumulation. Mice lacking most abundant protein, proteolipid protein (PLP), are fully myelinated, but PLP‐deficient exhibits reduced content. We therefore hypothesized that “high...
Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by age-dependent seroprevalence (up to >20%) functional NMDAR1-AB all immunoglobulin classes found in >5000 individuals, healthy or affected different diseases. These findings question a merely encephalitogenic role NMDAR1-AB. Here, we show that belong normal autoimmune repertoire dogs, cats, rats, mice,...
To maintain homeostasis, the body, including brain, reprograms its metabolism in response to altered nutrition or disease. However, consequences of these challenges for energy different brain cell types remain unknown. Here, we generated a proteome atlas major central nervous system (CNS) from young and adult mice, after feeding therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) during neuroinflammation. Under steady-state conditions, CNS prefer distinct modes...
Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure denuded axons immune-mediated damage. Therefore, myelin widely considered be a protective structure for in sclerosis. Myelinated also depend on oligodendrocytes, which provide metabolic structural support axonal compartment. Given that pathology already visible at early disease stages, before overt demyelination, we reasoned autoimmune inflammation may disrupt oligodendroglial...
Abstract Oligodendrocytes and astrocytes are metabolically coupled to neuronal compartments. Pyruvate lactate can shuttle between glial cells axons via monocarboxylate transporters. However, only be synthesized or used in metabolic reactions with the help of dehydrogenase (LDH), a tetramer LDHA LDHB subunits varying compositions. Here we show that mice cell type‐specific disruption both Ldha Ldhb genes oligodendrocytes lack pathological phenotype would indicative oligodendroglial...
Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension the glial cell membrane with characteristic composition proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention disease, presumably attributable to failure misfolded pass ER quality control. Because many partition into rafts, their interaction cholesterol could potentially be part control system. Here, we provide vitro vivo evidence that...
Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and adult, brain cholesterol derived from local synthesis not taken up circulation. However, contribution neurons glial cells to total metabolism unknown. Using conditional gene inactivation mouse, we disrupted squalene synthase (fdft1), which critical for synthesis, cerebellar granule some precerebellar nuclei. Mutant mice showed no histological signs neuronal...
Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to metabolism unknown. To investigate whether cortical projection neurons vivo essentially require biosynthesis which support neurons, we have conditionally ablated these mice either embryonically or postnatally. We found that synthesize during their entire lifetime. At stages, they can...