Ryazanov, Sergey

[["dc.bibliographiccitation.firstpage","E4971"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","E4977"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Turriani, Elisa"],["dc.contributor.author","Lázaro, Diana F."],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Schön, Margarete"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Arndt-Jovin, Donna J."],["dc.contributor.author","Becker, Dorothea"],["dc.date.accessioned","2018-04-23T11:47:36Z"],["dc.date.available","2018-04-23T11:47:36Z"],["dc.date.issued","2017"],["dc.description.abstract","Recent epidemiological and clinical studies have reported a significantly increased risk for melanoma in people with Parkinson’s disease. Because no evidence could be obtained that genetic factors are the reason for the association between these two diseases, we hypothesized that of the three major Parkinson’s disease-related proteins—α-synuclein, LRRK2, and Parkin—α-synuclein might be a major link. Our data, presented here, demonstrate that α-synuclein promotes the survival of primary and metastatic melanoma cells, which is the exact opposite of the effect that α-synuclein has on dopaminergic neurons, where its accumulation causes neuronal dysfunction and death. Because this detrimental effect of α-synuclein on neurons can be rescued by the small molecule anle138b, we explored its effect on melanoma cells. We found that treatment with anle138b leads to massive melanoma cell death due to a major dysregulation of autophagy, suggesting that α-synuclein is highly beneficial to advanced melanoma because it ensures that autophagy is maintained at a homeostatic level that promotes and ensures the cell’s survival."],["dc.identifier.doi","10.1073/pnas.1700200114"],["dc.identifier.gro","3142238"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13362"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0027-8424"],["dc.title","Treatment with diphenyl–pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","924"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Neuropathology and Experimental Neurology"],["dc.bibliographiccitation.lastpage","933"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Shi, Song"],["dc.contributor.author","Wagner, Jens"],["dc.contributor.author","Mitteregger-Kretzschmar, Gerda"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.date.accessioned","2017-09-07T11:43:35Z"],["dc.date.available","2017-09-07T11:43:35Z"],["dc.date.issued","2015"],["dc.description.abstract","Prion diseases are fatal neurodegenerative diseases characterized by accumulation of the pathogenic prion protein PrPSc in the brain. We established quantitative real-time quaking-induced conversion for the measurement of minute amounts of PrPSc in body fluids such as urine. Using this approach, we monitored the efficacy of antiprion therapy by quantifying the seeding activity of PrPSc from the brain and urine of mice after prion infection. We found that the aggregation inhibitor anle138b decreased the levels of PrPSc in the brain and urine. Importantly, variations of PrPSc levels in the urine closely corresponded to those in the brain. Our findings indicate that quantification of urinary PrPSc enables measurement of prion disease progression in body fluids and can substitute for immunodetection in brain tissue. We expect PrPSc quantification biologic fluids (such as urine and cerebrospinal fluid) with quantitative real-time quaking-induced conversion to emerge as a valuable noninvasive diagnostic tool for monitoring disease progression and the efficacy of therapeutic approaches in animal studies and human clinical trials of prion diseases. Moreover, highly sensitive methods for quantifying pathologic aggregate seeds might provide novel molecular biomarkers for other neurodegenerative diseases that may involve prion-like mechanisms (protein aggregation and spreading), such as Alzheimer disease and Parkinson disease."],["dc.identifier.doi","10.1097/NEN.0000000000000233"],["dc.identifier.gro","3141840"],["dc.identifier.isi","000360142900007"],["dc.identifier.pmid","26247395"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1656"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0022-3069"],["dc.title","Quantitative Real-Time Quaking-Induced Conversion Allows Monitoring of Disease-Modifying Therapy in the Urine of Prion-Infected Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","800"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - General Subjects"],["dc.bibliographiccitation.lastpage","807"],["dc.bibliographiccitation.volume","1862"],["dc.contributor.author","Reiner, Anne M."],["dc.contributor.author","Schmidt, Felix"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Weckbecker, Daniel"],["dc.contributor.author","Deeg, Andreas A."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Zinth, Wolfgang"],["dc.date.accessioned","2018-01-17T11:27:13Z"],["dc.date.available","2018-01-17T11:27:13Z"],["dc.date.issued","2017"],["dc.description.abstract","Recently diphenyl-pyrazole (DPP) compounds and especially anle138b were found to reduce the aggregation of α-synuclein or Tau protein in vitro as well as in a mouse model of neurodegenerative diseases . Direct interaction of the DPPs with the fibrillar structure was identified by fluorescence spectroscopy. Thereby a strong dependence of the fluorescence on the surroundings could be identified ."],["dc.identifier.doi","10.1016/j.bbagen.2017.12.007"],["dc.identifier.pmid","29273222"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11675"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Photophysics of diphenyl-pyrazole compounds in solutions and α-synuclein aggregates"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1884"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - General Subjects"],["dc.bibliographiccitation.lastpage","1890"],["dc.bibliographiccitation.volume","1850"],["dc.contributor.author","Deeg, Andreas A."],["dc.contributor.author","Reiner, Anne M."],["dc.contributor.author","Schmidt, Felix"],["dc.contributor.author","Schueder, Florian"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Ruf, Viktoria C."],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Zinth, Wolfgang"],["dc.date.accessioned","2017-09-07T11:43:35Z"],["dc.date.available","2017-09-07T11:43:35Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Special diphenyl-pyrazole compounds and in particular anle138b were found to reduce the progression of prion and Parkinson's disease in animal models. The therapeutic impact of these compounds was attributed to the modulation of a-synuclein and prion-protein aggregation related to these diseases. Methods: Photophysical and photochemical properties of the diphenyl-pyrazole compounds anle138b, anle186b and sery313b and their interaction with monomeric and aggregated a-synuclein were studied by fluorescence techniques. Results: The fluorescence emission of diphenyl-pyrazole is strongly increased upon incubation with a-synuclein fibrils, while no change in fluorescence emission is found when brought in contact with monomeric a-synuclein. This points to a distinct interaction between diphenyl-pyrazole and the fibrillar structure with a high binding affinity (K-d = 190 +/- 120 nM) for anle138b. Several a-synuclein proteins form a hydrophobic binding pocket for the diphenyl-pyrazole compound. A UV-induced dehalogenation reaction was observed for anle138b which is modulated by the hydrophobic environment of the fibrils. Conclusion: Fluorescence of the investigated diphenyl-pyrazole compounds strongly increases upon binding to fibrillar a-synuclein structures. Binding at high affinity occurs to hydrophobic pockets in the fibrils. General significance: The observed particular fluorescence properties of the diphenyl-pyrazole molecules open new possibilities for the investigation of the mode of action of these compounds in neurodegenerative diseases. The high binding affinity to aggregates and the strong increase in fluorescence upon binding make the compounds promising fluorescence markers for the analysis of aggregation-dependent epitopes. (C) 2015 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.bbagen.2015.05.021"],["dc.identifier.gro","3141841"],["dc.identifier.isi","000359173900026"],["dc.identifier.pmid","26028294"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1667"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1872-8006"],["dc.relation.issn","0304-4165"],["dc.title","Anle138b and related compounds are aggregation specific fluorescence markers and reveal high affinity binding to ot-synuclein aggregates"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","560a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dervisoglu, Riza"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Wegstroth, Melanie"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Lee, Joon"],["dc.contributor.author","Lal, Ratneshwar"],["dc.contributor.author","Eichele, Gregor"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2022-03-01T11:44:59Z"],["dc.date.available","2022-03-01T11:44:59Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.bpj.2017.11.3064"],["dc.identifier.pii","S0006349517342960"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103181"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","The Small Molecule anle138b Shows Interaction with α-Synuclein Oligomers in Phospholipid Membranes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3815"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","ACS Chemical Neuroscience"],["dc.bibliographiccitation.lastpage","3829"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ghio, Stephanie"],["dc.contributor.author","Camilleri, Angelique"],["dc.contributor.author","Caruana, Mario"],["dc.contributor.author","Ruf, Viktoria C."],["dc.contributor.author","Schmidt, Felix"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Cauchi, Ruben J."],["dc.contributor.author","Kamp, Frits"],["dc.contributor.author","Vassallo, Neville"],["dc.date.accessioned","2022-03-01T11:45:41Z"],["dc.date.available","2022-03-01T11:45:41Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1021/acschemneuro.9b00320"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103413"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1948-7193"],["dc.relation.issn","1948-7193"],["dc.title","Cardiolipin Promotes Pore-Forming Activity of Alpha-Synuclein Oligomers in Mitochondrial Membranes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Dervişoğlu, Rıza"],["dc.contributor.author","Frieg, Benedikt"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Nimerovsky, Evgeny"],["dc.contributor.author","Sant, Vrinda"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Andreas, Loren B."],["dc.date.accessioned","2022-10-04T10:21:08Z"],["dc.date.available","2022-10-04T10:21:08Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Aggregation of amyloidogenic proteins is a characteristic of multiple neurodegenerative diseases. Atomic resolution of small molecule binding to such pathological protein aggregates is of interest for the development of therapeutics and diagnostics. Here we investigate the interaction between α-synuclein fibrils and anle138b, a clinical drug candidate for disease modifying therapy in neurodegeneration and a promising scaffold for positron emission tomography tracer design. We used nuclear magnetic resonance spectroscopy and the cryogenic electron microscopy structure of α-synuclein fibrils grown in the presence of lipids to locate anle138b within a cavity formed between two β-strands. We explored and quantified multiple binding modes of the compound in detail using molecular dynamics simulations. Our results reveal stable polar interactions between anle138b and backbone moieties inside the tubular cavity of the fibrils. Such cavities are common in other fibril structures as well."],["dc.identifier.doi","10.1038/s41467-022-32797-w"],["dc.identifier.pii","32797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114336"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","420a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Sadasivam, Saravanan Manikam"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Roeters, Steven"],["dc.contributor.author","Wouterson, Sander"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Killian, J. Antoinette"],["dc.date.accessioned","2017-09-07T11:52:26Z"],["dc.date.available","2017-09-07T11:52:26Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1016/j.bpj.2015.11.2271"],["dc.identifier.gro","3144934"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2613"],["dc.notes.intern","Crossref Import"],["dc.notes.status","public"],["dc.publisher","Elsevier BV"],["dc.relation.issn","0006-3495"],["dc.title","Effect of the Novel Amyloid Inhibitor “anle145c” on Aggregation of Islet Amyloid Polypeptide and how it is Modulated by Membranes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","256a"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Saravanan, Manikam Sadasivam"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Seeliger, Janine"],["dc.contributor.author","Winter, Roland"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Killian, J. Antoinette"],["dc.date.accessioned","2022-03-01T11:44:58Z"],["dc.date.available","2022-03-01T11:44:58Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.1016/j.bpj.2014.11.1416"],["dc.identifier.pii","S0006349514026253"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103177"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","The Novel Inhibitor “Anle145C” Efficiently Inhibits Fibril Formation of Islet Amyloid Polypeptide (IAPP) and uses Distinctly Different Modes of Action in the Absence and Presence of Membranes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","38"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Translational Neurodegeneration"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Lemos, Miguel"],["dc.contributor.author","Venezia, Serena"],["dc.contributor.author","Refolo, Violetta"],["dc.contributor.author","Heras-Garvin, Antonio"],["dc.contributor.author","Schmidhuber, Sabine"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Galabova, Gergana"],["dc.contributor.author","Stefanova, Nadia"],["dc.date.accessioned","2022-03-01T11:43:59Z"],["dc.date.available","2022-03-01T11:43:59Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Background Misfolded oligomeric α-synuclein plays a pivotal role in the pathogenesis of α-synucleinopathies including Parkinson’s disease and multiple system atrophy, and its detection parallels activation of microglia and a loss of neurons in the substantia nigra pars compacta. Here we aimed to analyze the therapeutic efficacy of PD03, a new AFFITOPE® immunotherapy approach, either alone or in combination with Anle138b, in a PLP-α-syn mouse model. Methods The PLP-α-syn mice were treated with PD03 immunotherapy, Anle138b, or a combination of two. Five months after study initiation, the mice underwent behavioral testing and were sacrificed for neuropathological analysis. The treatment groups were compared to the vehicle group with regard to motor performance, nigral neuronal loss, microglial activation and α-synuclein pathology. Results The PLP-α-syn mice receiving the PD03 or Anle138b single therapy showed improvement of gait deficits and preservation of nigral dopaminergic neurons associated with the reduced α-synuclein oligomer levels and decreased microglial activation. The combined therapy with Anle138b and PD03 resulted in lower IgG binding in the brain as compared to the single immunotherapy with PD03. Conclusions PD03 and Anle138b can selectively target oligomeric α-synuclein, resulting in attenuation of neurodegeneration in the PLP-α-syn mice. Both approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies."],["dc.description.abstract","Abstract Background Misfolded oligomeric α-synuclein plays a pivotal role in the pathogenesis of α-synucleinopathies including Parkinson’s disease and multiple system atrophy, and its detection parallels activation of microglia and a loss of neurons in the substantia nigra pars compacta. Here we aimed to analyze the therapeutic efficacy of PD03, a new AFFITOPE® immunotherapy approach, either alone or in combination with Anle138b, in a PLP-α-syn mouse model. Methods The PLP-α-syn mice were treated with PD03 immunotherapy, Anle138b, or a combination of two. Five months after study initiation, the mice underwent behavioral testing and were sacrificed for neuropathological analysis. The treatment groups were compared to the vehicle group with regard to motor performance, nigral neuronal loss, microglial activation and α-synuclein pathology. Results The PLP-α-syn mice receiving the PD03 or Anle138b single therapy showed improvement of gait deficits and preservation of nigral dopaminergic neurons associated with the reduced α-synuclein oligomer levels and decreased microglial activation. The combined therapy with Anle138b and PD03 resulted in lower IgG binding in the brain as compared to the single immunotherapy with PD03. Conclusions PD03 and Anle138b can selectively target oligomeric α-synuclein, resulting in attenuation of neurodegeneration in the PLP-α-syn mice. Both approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies."],["dc.identifier.doi","10.1186/s40035-020-00217-y"],["dc.identifier.pii","217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102892"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","2047-9158"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]