A5048745413- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Nerve injury and regeneration
- Botulinum Toxin and Related Neurological Disorders
- Genetic Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Long-Term Effects of COVID-19
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Restless Legs Syndrome Research
- Health Systems, Economic Evaluations, Quality of Life
- Neurological diseases and metabolism
- Multiple Sclerosis Research Studies
- Nuclear Receptors and Signaling
- Dysphagia Assessment and Management
- Autism Spectrum Disorder Research
- Signaling Pathways in Disease
- COVID-19 and Mental Health
- Cerebral Palsy and Movement Disorders
- Axon Guidance and Neuronal Signaling
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
- Clinical Reasoning and Diagnostic Skills
Ruhr University Bochum
2016-2025
St. Josef-Hospital
2017-2025
Springer Nature (Germany)
2022
Deutsche Nationalbibliothek
2022
Metropolitan University
2020
Klinik und Poliklinik für Neurologie
2020
CS Diagnostics
2019
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2007-2017
Universitätsmedizin Göttingen
2010-2016
University of Göttingen
2006-2013
Axonal degeneration is an initial key step in traumatic and neurodegenerative CNS disorders. We established a unique vivo epifluorescence imaging paradigm to characterize very early events axonal the rat optic nerve. Single retinal ganglion cell axons were visualized by AAV-mediated expression of dsRed this allowed quantification postlesional acute (AAD). EM analysis revealed severe structural alterations cytoskeleton, cytoplasmatic vacuolization, appearance autophagosomes within first hours...
Functional regeneration in the CNS is limited by lesion-induced neuronal apoptosis and an environment inhibiting axonal elongation. A principal, yet unresolved question interaction between these two major factors. We thus evaluated role of pharmacological inhibition rho kinase (ROCK), a key mediator myelin-derived growth CNTF, potent neurotrophic factor for retinal ganglion cells (RGC), models cell neurite outgrowth/regeneration vitro vivo. Here, we show first time that ROCK inhibitor...
The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival neurons. However, as none these drugs completely target specific, it remains unclear how are mediated whether ROCK really most relevant pathway. To answer questions, we generated adeno-associated viral vectors to...
Axonal degeneration is one of the earliest features Parkinson's disease pathology, which followed by neuronal death in substantia nigra and other parts brain. Inhibition axonal combined with cellular neuroprotection therefore seem key to targeting an early stage progression. Based on our previous studies traumatic neurodegenerative models, we have identified rho kinase as a molecular target that can be manipulated disinhibit regeneration improve survival lesioned central nervous system...
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, yet disease-modifying treatments do not currently exist. Rho-associated protein kinase (ROCK) was recently described as a novel neuroprotective target in PD. Since alpha-synuclein (α-Syn) aggregation major hallmark pathogenesis of PD, we aimed to evaluate anti-aggregative potential pharmacological ROCK inhibition using isoquinoline derivative Fasudil, small molecule inhibitor already approved for clinical use...
Spinal muscular atrophy (SMA), a frequent neurodegenerative disease, is caused by reduced levels of functional survival motoneuron (SMN) protein. SMN involved in multiple pathways, including RNA metabolism and splicing as well development function. Here we provide evidence for major contribution the Rho-kinase (ROCK) pathway SMA pathogenesis. Using an vivo protein interaction system based on SUMOylation proteins, found that directly interacting with profilin2a. Profilin2a binds to stretch...
Abstract Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals axons precedes demise neurons in substantia nigra, which finally results clinical symptoms Parkinson disease (PD). The mechanisms underlying this early axonal are, however, still poorly understood. Here, we examined effects overexpression human wildtype alpha-synuclein ( α Syn-WT), a protein associated with PD, its mutant variants Syn-A30P -A53T on neurite morphology functional...
Disease progression in amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons (MN) and their axons, but also influenced neighboring cells such as astrocytes microglial cells. The role microglia ALS complex it switches from an anti‐inflammatory neuroprotective phenotype early disease to a proinflammatory neurotoxic later stages. Our previous studies models neurodegeneration identified rho kinase (ROCK) target, which can be manipulated beneficially influence...
The impact of the gut microbiome is being increasingly appreciated in health and various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). In pathogenesis PD, role has been previously established. conjunction with a better understanding intestinal microbiome, link to misfolding spread alpha-synuclein via inflammatory processes within discussed. case-control study, we assessed 54 PD patients 32 healthy controls (HC). Additionally, tested this...
Abstract Introduction The aim of this German national guideline is to optimize the clinical care patients with Parkinson's disease (PD) in terms diagnostics, drug and surgical treatment care. Summary or definition topic This guidance was prepared for Society Neurology (DGN) collaboration Austrian (ÖGN) Swiss Neurological (SNG) German-speaking countries. guidelines diagnosis PD have been revised by a expert group commission DGN at S2k level. main objective these regarding diagnosis, including...
Regenerative failure in the CNS largely depends on pronounced growth inhibitory signaling and reduced cellular survival after a lesion stimulus. One key mediator of is Rho-associated kinase (ROCK), which has been shown to modulate cone stability by regulation actin dynamics. Recently, there accumulating evidence ROCK also plays deleterious role for survival. In this manuscript we illustrate that involved variety intracellular pathways comprise far more than those neurite inhibition alone....
Novel therapeutic concepts against cerebral ischemia focus on cell-based therapies in order to overcome some of the side effects thrombolytic therapy. However, are hampered because restricted understanding regarding optimal cell transplantation routes and due low survival rates grafted cells. We therefore transplanted adult green fluorescence protein positive neural precursor cells (NPCs) either intravenously (systemic) or intrastriatally (intracerebrally) 6 hours after stroke mice. To...
Impulse control disorders (ICD), psychosis and delirium are part of the spectrum behavioural changes associated with Parkinson's disease (PD). The diagnostic therapeutic management these rather complex neuropsychiatric conditions has been updated in clinical guideline by German Society Neurology (DGN).
RNA interference (RNAi) provides a powerful experimental tool for sequence-specific gene silencing, allowing efficient analysis of function in multitude cell types. However, application RNAi primary mammalian neurons has been limited by low-transfection efficiency and considerable toxicity conventional transfection methods. In this study, we evaluated peptide-mediated polymer/lipid-based cellular delivery method siRNA into rat compared the results with commonly used liposomal reagent....
Abstract Parkinson’s disease is characterized by the progressive loss of dopaminergic (DA) neurons in substantia nigra. The heat‐shock protein 70 (Hsp70) reduces misfolding and aggregation. It has been shown to protect cells against oxidative stress apoptotic stimuli various neurodegenerative models. To deliver Hsp70 across cellular membranes into brain, we linked it a cell‐penetrating peptide derived from HIV trans‐activator transcription (Tat) protein. In vitro , Tat‐Hsp70 transduced...
Cerebral ischemia stimulates endogenous neurogenesis within the subventricular zone and hippocampal dentate gyrus of adult rodent brain. However, such newly generated cells soon die after cerebral ischemia. To enhance postischemic survival neural precursor (NPC) long-lasting regeneration, we applied antiapoptotic chaperone heat shock protein 70 (Hsp70) fused to a cell-penetrating peptide derived from HIV TAT ensure delivery across blood-brain barrier cell membrane. After transient focal in...
Improved survival of injured neurons and the inhibition repulsive environmental signalling are prerequisites for functional regeneration. BAG1 (Bcl-2-associated athanogene-1) is an Hsp70/Hsc70-binding protein, which has been shown to suppress apoptosis enhance neuronal differentiation. We investigated as a therapeutic molecule in lesioned visual system vivo. Using adeno-associated viral vector, (AAV.BAG1) was expressed retinal ganglion cells (RGC) then tested models optic nerve axotomy...