Gerhardt, Ellen

[["dc.bibliographiccitation.firstpage","123"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","133"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Straten, G"],["dc.contributor.author","Schmeer, C."],["dc.contributor.author","Kretz, A."],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Kugler, S."],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Gravel, C."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Isenmann, Stefan"],["dc.date.accessioned","2017-09-07T11:45:15Z"],["dc.date.available","2017-09-07T11:45:15Z"],["dc.date.issued","2002"],["dc.description.abstract","Following transection of the optic nerve (ON) in the adult rat, retinal ganglion cells (RGCs) undergo degeneration, and within 14 days 85% of axotomized RGCs die by apoptosis. Adenoviral delivery of the mammalian caspase inhibitor X-chromosome-linked inhibitor of apoptosis (Ad.XIAP) to the ON stump leads to expression exclusively in RGCs and rescues 18.9% of the RGCs that would degenerate without treatment. Following adenoviral vector injection into the vitreous body, bioactive glial cell line-derived neurotrophic factor (Ad.GDNF) is expressed in the retina and secreted to rescue 22.8% of lesioned RGCs. Here we report that coadministration of Ad.XIAP retrogradely directed to RGCs and intravitreal Ad.GDNF acts synergistically to protect axotomized RGCs. Combination treatment rescued 47.3% of RGCs that would undergo apoptosis without any treatment as opposed to 37.4% that would be expected if the two treatments acted independently. While without treatment only 15% of axotomized RGCs would survive, combination treatment resulted in survival of 55.4% of the total RGC population. These findings underline the neuroprotective potential of synergistic effects of a combination of different treatment strategies. (C) 2002 Elsevier Science (USA)."],["dc.identifier.doi","10.1006/nbdi.2002.0543"],["dc.identifier.gro","3144173"],["dc.identifier.isi","000179314100011"],["dc.identifier.pmid","12460552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1768"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0969-9961"],["dc.title","Potential synergistic protection of retinal ganglion cells from axotomy-induced apoptosis by adenoviral administration of glial cell line-derived neurotrophic factor and X-chromosome-linked inhibitor of apoptosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3124"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","3135"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Guerreiro, P. S."],["dc.contributor.author","Gerhardt, E."],["dc.contributor.author","Da Fonseca, T. L."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Outeiro, T. F."],["dc.contributor.author","Eckermann, Katrin"],["dc.date.accessioned","2017-09-07T11:44:49Z"],["dc.date.available","2017-09-07T11:44:49Z"],["dc.date.issued","2016"],["dc.description.abstract","Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known as the most frequent cause of familial Parkinson's disease (PD), but are also present in sporadic cases. The G2019S-LRRK2 mutation is located in the kinase domain of the protein, and has consistently been reported to promote a gain of kinase function. Several proteins have been reported as LRRK2 substrates and/or interactors, suggesting possible pathways involved in neurodegeneration in PD. Hyperphosphorylated Tau protein accumulates in neurofibrillary tangles, a typical pathological hallmark in Alzheimer's disease and frontotemporal dementia. In addition, it is also frequently found in the brains of PD patients. Although LRRK2 is a kinase, it appears that a putative interaction with Tau is phosphorylation-independent. However, the underlying mechanisms and the cellular consequences of this interaction are still unclear. In this study, we demonstrate an interaction between LRRK2 and Tau and that LRRK2 promotes the accumulation of non-monomeric and high-molecular weight (HMW) Tau species independent of its kinase activity. Interestingly, we found that LRRK2 increases Tau secretion, possibly as a consequence of an impairment of Tau proteasomal degradation. Our data highlight a mechanism through which LRRK2 regulates intracellular Tau levels, contributing to the progression of the pathology caused by the LRRK2-mediated proteasome impairment. In total, our findings suggest that the interplay between LRRK2 and proteasome activity might constitute a valid target for therapeutic intervention in PD."],["dc.identifier.doi","10.1007/s12035-015-9209-z"],["dc.identifier.gro","3141658"],["dc.identifier.isi","000377935400034"],["dc.identifier.pmid","26014385"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6231"],["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","1559-1182"],["dc.relation.issn","0893-7648"],["dc.subject","LRRK2; Tau Protein accumulation; Protein degradation"],["dc.title","LRRK2 Promotes Tau Accumulation, Aggregation and Release"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","189"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","197"],["dc.bibliographiccitation.volume","271"],["dc.contributor.author","Muth, Ingrid E."],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Kleinschnitz, Konstanze"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Balcarek, Peter"],["dc.contributor.author","Schreiber-Katz, Olivia"],["dc.contributor.author","Zierz, Stephan"],["dc.contributor.author","Dalakas, Marinas C."],["dc.contributor.author","Voll, Reinhard E."],["dc.contributor.author","Schmidt, Jens"],["dc.date.accessioned","2018-11-07T09:52:13Z"],["dc.date.available","2018-11-07T09:52:13Z"],["dc.date.issued","2015"],["dc.description.abstract","Inflammation is associated with protein accumulation in IBM, but precise mechanisms are elusive. The \"alarmin\" HMGB1 is upregulated in muscle inflammation. Its receptor RAGE is crucial for S-amyloid-associated neurodegeneration. Relevant signaling via HMGB1/RAGE is expected in IBM pathology. By real-time-PCR, mRNA-expression levels of HMGB1 and RAGE were upregulated in muscle biopsies of patients with IBM and PM, but not in muscular dystrophy or non-myopathic controls. By immunohistochemistry, both molecules displayed the highest signal in IBM, where they distinctly co-localized to intra-fiber accumulations of beta-amyloid and neurofilament/tau. In these fibers, identification of phosphorylated Erk suggested that relevant downstream activation is present upon HMGB1 signaling via RAGE. Protein expressions of HMGB1, RAGE, Erk and phosphorylated Erk were confirmed by Western blot. In a well established cell-culture model for pro-inflammatory cell-stress, exposure of human muscle-cells to 1L-1 beta + IFN-gamma induced cytoplasmic translocation of HMGB1 and subsequent release as evidenced by ELISA. Upregulation of RAGE on the cell surface was demonstrated by immunocytochemistry and flow-cytometry. Recombinant HMGB1 was equally potent as IL-1 beta + IFN-gamma in causing amyloid-accumulation and cell-death, and both were abrogated by the HMGB1-blocker BoxA. The findings strengthen the concept of unique interactions between degenerative and inflammatory mechanisms and suggest that HMGB1/RAGE signaling is a critical pathway in IBM pathology. (C) 2015 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Association Francaise contre les Myopathies (AFM) [13512, 14952]"],["dc.identifier.doi","10.1016/j.expneurol.2015.05.023"],["dc.identifier.isi","000362627200020"],["dc.identifier.pmid","26048613"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36071"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1090-2430"],["dc.relation.issn","0014-4886"],["dc.title","HMGB1 and RAGE in skeletal muscle inflammation: Implications for protein accumulation in inclusion body myositis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","225"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","233"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Reich, Arno"],["dc.contributor.author","Spering, Christopher"],["dc.contributor.author","Gertz, Karen"],["dc.contributor.author","Harms, Christoph"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Kronenberg, Golo"],["dc.contributor.author","Nave, Klaus A."],["dc.contributor.author","Schwab, Markus"],["dc.contributor.author","Tauber, Simone C."],["dc.contributor.author","Drinkut, Anja"],["dc.contributor.author","Harms, Kristian"],["dc.contributor.author","Beier, Chrstioph P."],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Endres, Matthias"],["dc.contributor.author","Schulz, Joerg B."],["dc.date.accessioned","2018-11-07T09:00:08Z"],["dc.date.available","2018-11-07T09:00:08Z"],["dc.date.issued","2011"],["dc.description.abstract","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 cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia."],["dc.identifier.doi","10.1523/JNEUROSCI.2188-10.2011"],["dc.identifier.isi","000285915100026"],["dc.identifier.pmid","21209208"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24077"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Fas/CD95 Regulatory Protein Faim2 Is Neuroprotective after Transient Brain Ischemia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","90"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of the Neurological Sciences"],["dc.bibliographiccitation.lastpage","95"],["dc.bibliographiccitation.volume","310"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2018-11-07T08:49:51Z"],["dc.date.available","2018-11-07T08:49:51Z"],["dc.date.issued","2011"],["dc.description.abstract","Cognitive dysfunction can be common among Parkinson's disease (PD) patients, and multiplication of the gene alpha-synuclein (alpha syn) increases the risk of dementia. Here, we studied the role of dopamine-depletion and increased asyn load and aggregation on cholinergic structures in vivo. Wild-type (WT) and mice with A30P asyn overexpression were treated subacutely with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MFTP), and the number of cholinergic cells in their nucleus basalis magnocellularis-substantia innominata (NBM-SI), their cortical fiber density and their expression of different genes 1 day or 90 days after the last MPTP-injection were measured. Long-term dopamine depletion decreased the expression of choline acetyl transferase (ChAT) in the NBM-SI of WT mice, but no neuron loss was observed. In contrast, cortical cholinergic fiber density was decreased three months after MPTP-injection. Increased brain-derived neurotrophic factor expression could maintain cholinergic functions under these conditions. Expression of A30P alpha syn in six-months-old transgenic mice resulted in decreased tyrosine receptor kinase B expression, and lower cortical cholinergic fiber density. Dopamine-depletion by MPTP induced cholinergic cell loss in the NBM-SI and increased cortical fiber loss. Our findings may explain why cholinergic cells are more vulnerable in PD, leading to an increased probability of dementia. (C) 2011 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jns.2011.06.048"],["dc.identifier.isi","000296927500023"],["dc.identifier.pmid","21774947"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21555"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","0022-510X"],["dc.title","Dopamine-depletion and increased alpha-synuclein load induce degeneration of cortical cholinergic fibers in mice"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","104721"],["dc.bibliographiccitation.journal","Journal of Proteomics"],["dc.bibliographiccitation.volume","269"],["dc.contributor.author","Brás, Inês C."],["dc.contributor.author","Khani, Mohammad H."],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Parfentev, Iwan"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","van Riesen, Christoph"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Gollisch, Tim"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2022-10-04T10:21:29Z"],["dc.date.available","2022-10-04T10:21:29Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100004939 Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und Molekulare Biowissenschaften"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100007601 Horizon 2020"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100000781 European Research Council"],["dc.identifier.doi","10.1016/j.jprot.2022.104721"],["dc.identifier.pii","S1874391922002457"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114423"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.issn","1874-3919"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Ectosomes and exosomes modulate neuronal spontaneous activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2331"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","2343"],["dc.bibliographiccitation.volume","586"],["dc.contributor.author","Kron, Miriam"],["dc.contributor.author","Reuter, Julia"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Dutschmann, Mathias"],["dc.date.accessioned","2018-11-07T11:15:39Z"],["dc.date.available","2018-11-07T11:15:39Z"],["dc.date.issued","2008"],["dc.description.abstract","The Kolliker-Fuse nucleus (KF) contributes essentially to respiratory pattern formation and adaptation of breathing to afferent information. Systems physiology suggests that these KF functions depend on NMDA receptors (NMDA-R). Recent investigations revealed postnatal changes in the modulation of glutamatergic neurotransmission by brain-derived neurotrophic factor (BDNF) in the KF. Therefore, we investigated postnatal changes in NMDA-R subunit composition and postsynaptic modulation of NMDA-R-mediated currents by BDNF in KF slice preparations derived from three age groups (neonatal: postnatal day (P) 1-5; intermediate: P6-13; juvenile: P14-21). Immunohistochemistry showed a developmental up-regulation of the NR2D subunit. This correlated with a developmental increase in decay time of NMDA currents and a decline of desensitization in response to repetitive exogenous NMDA applications. Thus, developmental up-regulation of the NR2D subunit, which reduces the Mg2+ block of NMDA-R, causes these specific changes in NMDA current characteristics. This may determine the NMDA-R-dependent function of the mature KF in the control of respiratory phase transition. Subsequent experiments revealed that bath-application of BDNF progressively potentiated these repetitively evoked NMDA currents only in intermediate and juvenile age groups. Pharmacological inhibition of protein kinase C (PKC), as a downstream component of the BDNF-tyrosine kinase B receptor (trkB) signalling, prevented BDNF-induced potentiation of NMDA currents. BDNF-induced potentiation of NMDA currents in later developmental stages might be essential for synaptic plasticity during the adaptation of the breathing pattern in response to peripheral/central commands. The lack of plasticity in neonatal neurones strengthens the hypothesis that the respiratory network becomes permissive for activity-dependent plasticity with ongoing postnatal development."],["dc.identifier.doi","10.1113/jphysiol.2007.148916"],["dc.identifier.isi","000255497900011"],["dc.identifier.pmid","18339694"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54416"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3751"],["dc.title","Emergence of brain-derived neurotrophic factor-induced postsynaptic potentiation of NMDA currents during the postnatal maturation of the Kolliker-Fuse nucleus of rat"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","25991"],["dc.bibliographiccitation.issue","51"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","26000"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Brasil, Aline de Araújo"],["dc.contributor.author","de Carvalho, Mariana Dias Castela"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Queiroz, Daniela Dias"],["dc.contributor.author","Pereira, Marcos Dias"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Eleutherio, Elis Cristina Araujo"],["dc.date.accessioned","2020-04-02T15:01:54Z"],["dc.date.available","2020-04-02T15:01:54Z"],["dc.date.issued","2019"],["dc.description.abstract","Mutations in Cu/Zn superoxide dismutase (Sod1) have been reported in both familial and sporadic amyotrophic lateral sclerosis (ALS). In this study, we investigated the behavior of heteromeric combinations of wild-type (WT) and mutant Sod1 proteins A4V, L38V, G93A, and G93C in human cells. We showed that both WT and mutant Sod1 formed dimers and oligomers, but only mutant Sod1 accumulated in intracellular inclusions. Coexpression of WT and hSod1 mutants resulted in the formation of a larger number of intracellular inclusions per cell than that observed in cells coexpressing WT or mutant hSod1. The number of inclusions was greater in cells expressing A4V hSod1. To eliminate the contribution of endogenous Sod1, and better evaluate the effect of ALS-associated mutant Sod1 expression, we expressed human Sod1 WT and mutants in human cells knocked down for endogenous Sod1 (Sod1-KD), and in sod1Δ yeast cells. Using Sod1-KD cells we found that the WT-A4V heteromers formed higher molecular weight species compared with A4V and WT homomers. Using the yeast model, in conditions of chronological aging, we concluded that cells expressing Sod1 heterodimers showed decreased antioxidant activity, increased oxidative damage, reduced longevity, and oxidative stress-induced mutant Sod1 aggregation. In addition, we also found that ALS-associated Sod1 mutations reduced nuclear localization and, consequently, impaired the antioxidant response, suggesting this change in localization may contribute to disease in familial ALS. Overall, our study provides insight into the molecular underpinnings of ALS and may open avenues for the design of future therapeutic strategies."],["dc.identifier.doi","10.1073/pnas.1902483116"],["dc.identifier.pmid","31796595"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63570"],["dc.language.iso","en"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.relation.issn","1091-6490"],["dc.title","Characterization of the activity, aggregation, and toxicity of heterodimers of WT and ALS-associated mutant Sod1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Journal of Parkinson's Disease"],["dc.bibliographiccitation.lastpage","26"],["dc.contributor.author","Brás, Inês C."],["dc.contributor.author","Khani, Mohammad H."],["dc.contributor.author","Vasili, Eftychia"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Parfentev, Iwan"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Fahlbusch, Christiane"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2022-11-01T10:17:15Z"],["dc.date.available","2022-11-01T10:17:15Z"],["dc.date.issued","2022"],["dc.description.abstract","Background: Various cellular pathways have been implicated in the transfer of disease-related proteins between cells, contributing to disease progression and neurodegeneration. However, the overall effects of protein transfer are still unclear. Objective: Here, we performed a systematic comparison of basic molecular mechanisms involved in the release of alpha-synuclein, Tau, and huntingtin, and evaluated functional effects upon internalization by receiving cells. Methods: Evaluation of protein release to the extracellular space in a free form and in extracellular vesicles using an optimized ultracentrifugation protocol. The extracellular effects of the proteins and extracellular vesicles in primary neuronal cultures were assessed using multi-channel electrophysiological recordings combined with a customized spike sorting framework. Results: We demonstrate cells differentially release free-forms of each protein to the extracellular space. Importantly, neuronal activity is distinctly modulated upon protein internalization in primary cortical cultures. In addition, these disease-related proteins also occur in extracellular vesicles, and are enriched in ectosomes. Internalization of ectosomes and exosomes by primary microglial or astrocytic cells elicits the production of pro-inflammatory cytokines, and modifies spontaneous electrical activity in neurons. Objective: Overall, our study demonstrates that released proteins can have detrimental effects for surrounding cells, and suggests protein release pathways may be exploited as therapeutic targets in different neurodegenerative diseases."],["dc.identifier.doi","10.3233/JPD-223516"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116767"],["dc.notes.intern","DOI-Import GROB-605"],["dc.relation.eissn","1877-718X"],["dc.relation.issn","1877-7171"],["dc.title","Molecular Mechanisms Mediating the Transfer of Disease-Associated Proteins and Effects on Neuronal Activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","591"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","600"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Kermer, Pawel"],["dc.contributor.author","Schulz, Joerg B."],["dc.date.accessioned","2018-11-07T09:16:15Z"],["dc.date.available","2018-11-07T09:16:15Z"],["dc.date.issued","2012"],["dc.description.abstract","Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons from the substantia nigra pars compacta (SNpc). alpha-synuclein (alpha syn) has been linked to the pathophysiology of PD, because of its mutations causing familial PD and its accumulation in brains of patients with familial and sporadic PD. Dopamine (DA) replacement is the most effective therapy for ameliorating the motor symptoms of PD; however, it remains controversial whether DA-replacement boosts regeneration in the dopaminergic system or accelerates disease progression and enhances neuronal loss. Here, we studied the effect of chronic L-DOPA treatment on dopaminergic neurons in wild-type (WT) and A30P alpha syn transgenic mice after MPTP treatment. Acute MPTP intoxication induced degeneration of dopaminergic neurons in both WT and A30P alpha syn transgenic mice. A strong regeneration of dopaminergic fibers at 90 days after MPTP was observed in WT mice. In contrast, regeneration was less pronounced in A30P alpha syn mice. Chronic L-DOPA treatment after MPTP intoxication did not only reduce the regeneration of nigrostriatal fibers but also led to an increased apoptotic gene-expression profile in the SNpc and to a decline of TH-positive neurons in A30P alpha syn. Our findings reveal that the presence of A30P alpha syn inhibits the regeneration of nigrostriatal dopaminergic fibers, and that L-DOPA treatment might interact with the pathogenesis in PD. (C) 2011 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2011.09.017"],["dc.identifier.isi","000297883500065"],["dc.identifier.pmid","22001606"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27892"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","0969-9961"],["dc.title","A30P alpha-synuclein impairs dopaminergic fiber regeneration and interacts with L-DOPA replacement in MPTP-treated mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]