A5034598333- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Genetic Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Cellular transport and secretion
- Cell death mechanisms and regulation
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Sirtuins and Resveratrol in Medicine
- Neurological disorders and treatments
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- RNA regulation and disease
- MicroRNA in disease regulation
- Hepatitis B Virus Studies
- Plant Gene Expression Analysis
- Lanthanide and Transition Metal Complexes
- Lysosomal Storage Disorders Research
- Signaling Pathways in Disease
- Hepatitis C virus research
- Botulinum Toxin and Related Neurological Disorders
Universidade Federal do Paraná
2025
University of Göttingen
2010-2024
Universitätsmedizin Göttingen
2015-2024
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2008-2022
University of Kurdistan
2022
University of Ottawa
2017
Ottawa Hospital
2017
Deutsche Forschungsgemeinschaft
2008
University of Tübingen
2001-2005
Hertie Institute for Clinical Brain Research
2004
Aggregation of alpha-synuclein (ASYN) in Lewy bodies and neurites is the typical pathological hallmark Parkinson's disease (PD) other synucleinopathies. Furthermore, mutations gene encoding for ASYN are associated with familial sporadic forms PD, suggesting this protein plays a central role disease. However, precise contribution to neuronal dysfunction death unclear. There intense debate about nature toxic species little known molecular determinants oligomerization aggregation cell. In order...
Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. 2 was previously shown modulate proteotoxicity age-associated neurodegenerative disorders such as Alzheimer Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into interplay between sirtuin α-synuclein, major component of pathognomonic protein inclusions in PD other synucleinopathies. We found that α-synuclein is...
The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, fibrillization of impair synaptic plasticity cause degeneration. However, pathology may also result in the loss specific physiological functions, which largely unknown but could contribute to neuronal dysfunction. In present study, we uncovered a novel function its ability regulate brain insulin...
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical, and neuropathological changes reminiscent of those occurring in idiopathic Parkinson's disease (PD). Here we show that a peptide caspase inhibitor, N-benzyloxy-carbonyl-val-ala-asp-fluoromethyl ketone, or adenoviral gene transfer (AdV) protein X-chromosome-linked inhibitor apoptosis (XIAP), prevent cell death dopaminergic substantia nigra pars compacta (SNpc) neurons induced by MPTP its active metabolite...
Brain-derived neurotrophic factor plays a key role in neuronal and axonal survival. is expressed the immune cells lesions of experimental autoimmune encephalomyelitis multiple sclerosis, thus potentially mediating neuroprotective effects. We investigated functional brain-derived myelin oligodendrocyte glycoprotein-induced encephalomyelitis, an animal model sclerosis. Mice deficient for displayed attenuated response acute phase but progressive disability with enhanced loss chronic disease. In...
Alpha-synuclein (aSyn) is a central player in Parkinson's disease (PD) but the precise molecular mechanisms underlying its pathogenicity remain unclear. It has recently been suggested that nuclear aSyn may modulate gene expression, possibly via interactions with DNA. However, biological behavior of nucleus and factors affecting transcriptional role are not known. Here, we investigated aSyn-mediated transcription deregulation by assessing effects impact phosphorylation these dynamics. We...
Alpha-synuclein (aSyn) is considered a major culprit in Parkinson's disease (PD) pathophysiology. However, the precise molecular function of protein remains elusive. Recent evidence suggests that aSyn may play role on transcription regulation, possibly by modulating acetylation status histones. Our study aimed at evaluating impact wild-type (WT) and mutant A30P gene expression, dopaminergic neuronal cell model, decipher potential mechanisms underlying aSyn-mediated transcriptional...
We have assessed the impact of α-synuclein overexpression on differentiation potential and phenotypic signatures two neural-committed induced pluripotent stem cell lines derived from a Parkinson's disease patient with triplication human SNCA genomic locus. In parallel, comparative studies were performed control healthy individuals generated iPS-derived neuroprogenitor infected lentivirus incorporating small hairpin RNA to knock down mRNA. The exhibited reduced capacity differentiate into...
Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes a number cellular processes, including mitochondrial integrity function. We used whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers human [A53T]α-Synuclein–induced neurotoxicity. Decreased expression chaperone tumor necrosis factor receptor protein-1 (TRAP1) was found enhance age-dependent loss head dopamine (DA) DA neuron resulting from...
Alpha-synuclein (aSyn) plays a crucial role in Parkinson's disease (PD) and other synucleinopathies, since it misfolds accumulates typical proteinaceous inclusions. While the function of aSyn is thought to be related vesicle binding trafficking, precise molecular mechanisms linking with synucleinopathies are still obscure. can spread prion-like manner between interconnected neurons, contributing propagation pathology progressive nature synucleinopathies. Here, we investigated interaction...
Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation α-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations biological properties. Recently, aSyn pathology was shown to spread between neurons in prion-like manner. Proteins like exhibit self-propagating capacity appear be able stable conformational states, known as strains, which modulated both environmental protein-intrinsic factors. Here, we...
Tau abnormalities play a central role in several neurodegenerative diseases, collectively known as tauopathies. In the present study, we examined whether mutant huntingtin (mHtt), which causes Huntington's disease (HD), modifies phosphorylation and subcellular localization using cell mouse HD models. Initially, used novel bimolecular fluorescence complementation assays live cells to evaluate interactions with either wild type (25QHtt) or (103QHtt). While 25QHtt interacted at level of...
Alpha-synuclein (aSyn) accumulates in intracellular inclusions synucleinopathies, but the molecular mechanisms leading to disease are unclear. We identify 10 kDa heat shock protein (HSP10) as a mediator of aSyn-induced mitochondrial impairments striatal synaptosomes. find an age-associated increase cytosolic levels HSP10, and concomitant decrease levels, aSyn transgenic mice. The superoxide dismutase 2, client HSP10/HSP60 folding complex, synaptosomal spare respiratory capacity also reduced....
Abstract Nuclear magnetic resonance (NMR) is widely applied from analytics to biomedicine although it an inherently insensitive phenomenon. Overcoming sensitivity challenges key further broaden the applicability of NMR and, for example, improve medical diagnostics. Here, we present a rapid strategy enhance signals 13 C‐labelled metabolites with para ‐hydrogen in particular, C‐pyruvate, important molecule energy metabolism. We succeeded obtain average 27 % C polarization 1‐ C‐pyruvate water...
Mutations in Cu/Zn superoxide dismutase (Sod1) have been reported both familial and sporadic amyotrophic lateral sclerosis (ALS). In this study, we investigated the behavior of heteromeric combinations wild-type (WT) mutant Sod1 proteins A4V, L38V, G93A, G93C human cells. We showed that WT formed dimers oligomers, but only accumulated intracellular inclusions. Coexpression hSod1 mutants resulted formation a larger number inclusions per cell than observed cells coexpressing or hSod1. The was...
Abstract Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic is linked cognitive deficits LBD. Here, we investigated pathological impact αSyn on hippocampal neurons. We report that either overexpression or pre-formed fibrils (PFFs) treatment triggers formation cofilin-actin rods, synapse disruptors, cultured neurons synucleinopathy mouse models LBD patients. In vivo,...
Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and proliferation. Identification regulatory proteins that control switch between apoptotic alternative DR opens new therapeutic opportunities. Fas inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor Fas/CD95-mediated apoptosis. To investigate its role during...
Biointerface decoration with ligands is a crucial requirement to modulate biodistribution, increase half-life, and provide navigation control for targeted micro- or nanostructured systems. To better the process of ligand functionalization over three-dimensional (3D) polyester surfaces, we report characterization hybrid proteins developed enhance anchoring efficiency polymeric surfaces preserve optimal spatial orientation: sfGFP, mRFP1, RBD were attached substrate binding domain (SBD) formed...