A5037729597- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- T-cell and B-cell Immunology
- Neurological disorders and treatments
- Immune Cell Function and Interaction
- Hereditary Neurological Disorders
- RNA regulation and disease
- Psoriasis: Treatment and Pathogenesis
- Cellular transport and secretion
- Monoclonal and Polyclonal Antibodies Research
- Alzheimer's disease research and treatments
- Pluripotent Stem Cells Research
- Rheumatoid Arthritis Research and Therapies
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Hippo pathway signaling and YAP/TAZ
- CAR-T cell therapy research
- Microtubule and mitosis dynamics
- Autoimmune and Inflammatory Disorders Research
- Carcinogens and Genotoxicity Assessment
- IL-33, ST2, and ILC Pathways
- Neuroscience and Neural Engineering
- Immunotherapy and Immune Responses
Friedrich-Alexander-Universität Erlangen-Nürnberg
2016-2025
Universitätsklinikum Erlangen
2013-2025
Schiller International University
2024
LMU Klinikum
2014
Ludwig-Maximilians-Universität München
2009-2013
Federal Ministry of Education and Research
2012
Center for Clinical Research (United States)
2012
Significance α-Synuclein (α-Syn) aggregation underlies neurodegeneration in synucleinopathies. However, the nature of α-Syn aggregates and their toxic mechanisms human pathology remains elusive. Here, we delineate a role oligomeric for axonal integrity neuronal models oligomers disrupt anterograde transport mitochondria by causing subcellular changes transport-regulating proteins energy deficits. An increase neurons finally results synaptic degeneration. Together, our data provide...
Chaperonins have classically been thought of as intracellular molecules involved in the correct folding proteins.Their expression is upregulated during times stress such heat (hence their common nomenclature shock proteins [HSP]), anoxia, hypoglycaemia and reactive oxygen species [1].These are conditions found infected tissues or with chronic inflammation rheumatoid synovium.In location they protect cell from apoptotic death due to stress.Increasingly chaperonins recognised subserve...
Abstract Mutations in the LRRK2 gene are most common cause of genetic Parkinson’s disease. Although mechanisms behind pathogenic effects mutations still not clear, data emerging from vitro and vivo models suggests roles regulating neuronal polarity, neurotransmission, membrane cytoskeletal dynamics protein degradation. We created mice lacking exon 41 that encodes activation hinge kinase domain LRRK2. have performed a comprehensive analysis these up to 20 months age, including evaluation...
The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, most frequent cause HSP. To understand how mutations SPG4 affect human neurons, we generated induced pluripotent stem cells (hiPSCs) from fibroblasts two patients carrying c.1684C>T nonsense mutation controls. These control hiPSCs were able to differentiate into neurons glia at...
α-Synuclein has been reported to be important in modulating brain plasticity and a key protein neurodegenerative diseases, including Lewy body dementia (LBD). We investigated how α-synuclein levels modulate adult neurogenesis the development of dendritic arborization spines dentate gyrus, which new neurons are constantly added. In human hippocampus, endogenous were increased LBD, numbers SOX2-positive cells decreased. whether newly generated modulated by α-synuclein, we found α/β-synuclein...
Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, precise knowledge about role spatacsin neurons is very limited. We for first time analyzed expression function human forebrain derived from pluripotent stem cells including lines two SPG11 patients controls. patients'-derived exhibited...
Abstract Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson’s disease. Nevertheless, the role aSyn physiology remains elusive. Thus, we addressed impact specifically on response to OS neural cells. We characterize a distinct type fragmentation, following H 2 O or 6-OHDA-induced OS, defined by spherically-shaped hyperpolarized mitochondria, termed “mitospheres”. Mitosphere formation mechanistically...
Because of the numerous targets microRNAs (miRNAs), functional dissection specific miRNA/mRNA interactions is important to understand complex miRNA regulatory mechanisms. Glycoprotein A repetitions predominant (GARP) specifically expressed on CD25(+) CD4 T cells upon their activation. GARP has a long 3' untranslated region containing five highly conserved regions suggesting regulation its expression. Although physiologically cell subset characterized by stringent control proliferation,...
Synucleinopathies comprise a group of neurodegenerative diseases associated with abnormal accumulation α-synuclein. One the key factors that contribute to progression synucleinopathies is neuroinflammation. However, role lymphocytes in like Parkinson's disease (PD) remains largely unclear.To investigate how impact synucleinopathies, human wild-type α-synuclein (WTS) transgenic mice were crossed lacking mature (Rag2(-/-)). In this vivo model, we quantified aggregation substantia nigra (SN)...
Microglia are the main immune cells of brain and express a large genetic pattern genes linked to Parkinson's disease risk alleles. Monocytes like microglia myeloid-lineage cells, raising questions extent which they share gene expression with whether already altered early in clinical course disease. To decipher monocytic signature disease, we performed RNA-seq applied two-sample Kolmogorov-Smirnov test identify differentially expressed between controls patients changes variability...
Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types turn senescent under neurodegenerative conditions. Senescent were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet difference between is unclear. We aimed characterize comparison investigate differences similarities. In a culture model human fetal we determined unique transcriptome distinct from which comprises dysregulated pathways. Both, activated...
Abstract Background The gut-brain axis has been increasingly recognized as a critical pathway linking Inflammatory Bowel Diseases (IBD) with neurodegenerative diseases. Chronic inflammation resulting from IBD can extend beyond the gut, and epidemiological data have also linked to increased prevalence of conditions like Parkinson’s disease (PD). However, exact mechanisms underlying this interconnection are largely unclear. We therefore investigated how gut-primed T cells patients may drive...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss mDANs has not been fully understood yet, cell type-specific vulnerability linked to unique intracellular milieu, influenced dopamine metabolism, high demand for mitochondrial activity,...
Abstract Recent studies demonstrate that brain infiltration of peripheral immune cells and their interaction with brain-resident contribute to Parkinson’s disease (PD). However, mechanisms T cell-brain cell communication are not fully elucidated models allowing investigation between required. In this study, we developed a three-dimensional (3D) model composed stem cell-derived human midbrain organoids (hMO) blood cells. We demonstrated consist multiple midbrain-specific types, study motility...
Gastrointestinal (GI) dysfunction emerges years before motor symptoms in Parkinson′s disease (PD), implicating the enteric nervous system (ENS) early progression. However, mechanisms linking PD hallmark protein, α-synuclein (α-syn), to ENS - and whether these are influenced by inflammation remains elusive. Using iPSC-derived neural lineages from patients with α-syn triplications, we reveal that TNF-α increases mitochondrial-α-syn interactions, disrupts malate-aspartate shuttle, forces a...
Abstract Objective To examine whether single‐nucleotide polymorphisms (SNPs) of the interleukin‐4 receptor gene IL4R influence susceptibility to, or radiographic progression in, rheumatoid arthritis (RA). Methods The contribution 2 SNPs (I50V and Q551R) in coding region to RA was analyzed by allele‐specific polymerase chain reaction a case–control study 471 patients 371 healthy controls. Patients with available radiographs hands feet obtained years after disease onset (n = 302) were...
Objective Mutations in the spastic paraplegia gene 11 (SPG11), encoding spatacsin, cause most frequent form of autosomal‐recessive complex hereditary (HSP) and juvenile‐onset amyotrophic lateral sclerosis (ALS5). When SPG11 is mutated, patients frequently present with paraparesis, a thin corpus callosum, cognitive impairment. We previously delineated neurodegenerative phenotype neurons these patients. In current study, we recapitulated early developmental phenotypes outlined their cellular...
Parkinson's disease (PD) is neuropathologically characterized by the loss of dopaminergic neurons and deposition aggregated alpha synuclein (aSyn). Mounting evidence suggests that neuritic degeneration precedes neuronal in PD. A possible underlying mechanism could be interference aSyn with microtubule organization development, as implied several studies using cell-free model systems. In this study, we investigate impact on overexpressing H4 neuroglioma cells midbrain (mDANs) generated from...