Lingor, Paul

[["dc.bibliographiccitation.artnumber","625"],["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Roser, Anna-Elisa"],["dc.contributor.author","Caldi Gomes, Lucas"],["dc.contributor.author","Schünemann, Jonas"],["dc.contributor.author","Maass, Fabian"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2019-07-09T11:45:52Z"],["dc.date.available","2019-07-09T11:45:52Z"],["dc.date.issued","2018"],["dc.description.abstract","Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Its main neuropathological hallmarks are the degeneration of dopaminergic neurons in the substantia nigra and alpha-synuclein containing protein inclusions, called Lewy Bodies. The diagnosis of idiopathic PD is still based on the assessment of clinical criteria, leading to an insufficient diagnostic accuracy. Additionally, there is no biomarker available allowing the prediction of the disease course or monitoring the response to therapeutic approaches. So far, protein biomarker candidates such as alpha-synuclein have failed to improve diagnosis of PD. Circulating microRNAs (miRNAs) in body fluids are promising biomarker candidates for PD, as they are easily accessible by nonor minimally-invasive procedures and changes in their expression are associated with pathophysiological processes relevant for PD. Advances in miRNA analysis methods resulted in numerous recent publications on miRNAs as putative biomarkers. Here, we discuss the applicability of different body fluids as sources for miRNA biomarkers, highlight technical aspects of miRNA analysis and give an overview on published studies investigating circulating miRNAs as biomarker candidates for diagnosis of PD and other Parkinsonian syndromes."],["dc.identifier.arxiv","30233304"],["dc.identifier.doi","10.3389/fnins.2018.00625"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15332"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59325"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/34"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B09: Cytoskelettale Veränderungen tragen zu synapto-axonalen Fehlfunktionen in Morbus Parkinson bei"],["dc.relation.eissn","1662-453X"],["dc.relation.issn","1662-453X"],["dc.relation.workinggroup","RG Lingor (Translational Neurodegeneration)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.subject.ddc","610"],["dc.title","Circulating miRNAs as Diagnostic Biomarkers for Parkinson’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","81"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","93"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Gadjanski, Ivana"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Williams, Sarah K."],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Knöferle, Johanna"],["dc.contributor.author","Sättler, Muriel B."],["dc.contributor.author","Fairless, Richard"],["dc.contributor.author","Hochmeister, Sonja"],["dc.contributor.author","Sühs, Kurt-Wolfram"],["dc.contributor.author","Michaelis, Thomas"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Storch, Maria K."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2019-07-09T11:52:52Z"],["dc.date.available","2019-07-09T11:52:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Objective: The aim of this study was to investigate the role of voltage-dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis. Methods: Calcium ion (Ca2 ) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese-enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N-type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using -conotoxin GVIA, an N-type specific blocker. Results: We observed that pathological Ca2 influx into ONs during optic neuritis is mediated via N-type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of 1B, the pore-forming subunit of N-type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N-type VDCCs for inflammation-induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with -conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals. Interpretation: We conclude that N-type VDCCs play an important role in inflammation-induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca2 influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage."],["dc.identifier.doi","10.1002/ ana.21668"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60296"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Role of N-Type Voltage-Dependent Calcium Channels in Autoimmune Optic Neuritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","293"],["dc.bibliographiccitation.journal","Frontiers in Neurology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Weber, Markus"],["dc.contributor.author","Camu, William"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Hilgers, Reinhard"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Neuwirth, Christoph"],["dc.contributor.author","Günther, René"],["dc.contributor.author","Benatar, Michael"],["dc.contributor.author","Kuzma-Kozakiewicz, Magdalena"],["dc.contributor.author","Bidner, Helen"],["dc.contributor.author","Blankenstein, Christiane"],["dc.contributor.author","Frontini, Roberto"],["dc.contributor.author","Ludolph, Albert"],["dc.contributor.author","Koch, Jan C."],["dc.date.accessioned","2019-07-09T11:51:01Z"],["dc.date.available","2019-07-09T11:51:01Z"],["dc.date.issued","2019"],["dc.description.abstract","Objectives: Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose fasudil as a disease-modifying therapy for ALS patients. Methods: ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect biological fluids to assess target engagement and evaluate potential biomarkers for disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6-18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France. Results and conclusions: The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor fasudil in early-stage ALS-patients that started patient recruitment in 2019."],["dc.identifier.doi","10.3389/fneur.2019.00293"],["dc.identifier.pmid","30972018"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59859"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","15"],["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Joppe, Karina"],["dc.contributor.author","Roser, Anna-Elisa"],["dc.contributor.author","Maass, Fabian"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2019-07-09T11:49:58Z"],["dc.date.available","2019-07-09T11:49:58Z"],["dc.date.issued","2019"],["dc.description.abstract","The homeostasis of iron is of fundamental importance in the central nervous system (CNS) to ensure biological processes such as oxygen transport, mitochondrial respiration or myelin synthesis. Dyshomeostasis and accumulation of iron can be observed during aging and both are shared characteristics of several neurodegenerative diseases. Iron-mediated generation of reactive oxygen species (ROS) may lead to protein aggregation and cellular toxicity. The process of misfolding and aggregation of neuronal proteins such as α-synuclein, Tau, amyloid beta (Aβ), TDP-43 or SOD1 is a common hallmark of many neurodegenerative disorders and iron has been shown to facilitate protein aggregation. Thus, both, iron and aggregating proteins are proposed to amplify their detrimental effects in the disease state. In this review, we give an overview on effects of iron on aggregation of different proteins involved in neurodegeneration. Furthermore, we discuss the proposed mechanisms of iron-mediated toxicity and protein aggregation emphasizing the red-ox chemistry and protein-binding properties of iron. Finally, we address current therapeutic approaches harnessing iron chelation as a disease-modifying intervention in neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis."],["dc.identifier.doi","10.3389/fnins.2019.00015"],["dc.identifier.pmid","30723395"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15821"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59666"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/15"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B09: Cytoskelettale Veränderungen tragen zu synapto-axonalen Fehlfunktionen in Morbus Parkinson bei"],["dc.relation.issn","1662-4548"],["dc.relation.workinggroup","RG Lingor (Translational Neurodegeneration)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The Contribution of Iron to Protein Aggregation Disorders in the Central Nervous System"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]