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| 2. |
- Angot, Elodie, et al.
(författare)
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Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Several people with Parkinson's disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture, α-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of α-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred α-synuclein. We now demonstrate frequent transfer of α-synuclein from a rat brain engineered to overexpress human α-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of α-synuclein. Thus, we present evidence both for the involvement of endocytosis in α-synuclein uptake in vivo, and for seeding of aggregation of endogenous α-synuclein in the recipient neuron by the transferred α-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted α-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of α-synuclein and therefore might retard progression of Parkinson neuropathology.
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| 3. |
- Barker, Roger A, et al.
(författare)
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Are Stem Cell-Based Therapies for Parkinson's Disease Ready for the Clinic in 2016?
- 2016
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 6:1, s. 57-63
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Tidskriftsartikel (refereegranskat)abstract
- Recent news of an impending clinical cell transplantation trial in Parkinson's disease using parthenogenetic stem cells as a source of donor tissue have raised hopes in the patient community and sparked discussion in the research community. Based on discussions held by a global collaborative initiative on translation of stem cell therapy in Parkinson's disease, we have identified a set of key questions that we believe should be addressed ahead of every clinical stem cell-based transplantation trial in this disorder. In this article, we first provide a short history of cell therapy in Parkinson's disease and briefly describe the current state-of-art regarding human stem cell-derived dopamine neurons for use in any patient trial. With this background information as a foundation, we then discuss each of the key questions in relation to the upcoming therapeutic trial and critically assess if the time is ripe for clinical translation of parthenogenetic stem cell technology in Parkinson's disease.
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| 4. |
- Barker, Roger A., et al.
(författare)
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GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop
- 2020
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 875-891
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Tidskriftsartikel (refereegranskat)abstract
- The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.
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| 6. |
- Björklund, Anders, et al.
(författare)
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Repairing the Parkinson Brain
- 2021
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 11:s2, s. 123-125
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Björklund, Emil, et al.
(författare)
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Analysis of protein-ligand interactions from titrations and nuclear magnetic resonance relaxation dispersions
- 2022
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 31:1, s. 301-307
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Tidskriftsartikel (refereegranskat)abstract
- We present PLIS, a publicly available, open-source software for the determination of protein-ligand dissociation constants that can be used to characterize biological processes or to shed light on biophysical aspects of interactions. PLIS can analyze data from titration experiments monitored by for instance fluorescence spectroscopy or from nuclear magnetic resonance relaxation dispersion experiments. In addition to analysis of experimental data, PLIS includes functionality for generation of synthetic data, useful for understanding how different parameters effect the data in order to better analyze experiments.
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| 8. |
- Björklund, Patrik, 1970-, et al.
(författare)
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A Column Generation Method for Spatial TDMA Scheduling in Ad Hoc Networks
- 2004
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Ingår i: Ad hoc networks. - : Elsevier BV. - 1570-8705 .- 1570-8713. ; 2:Issue 4, s. 405-418
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Tidskriftsartikel (refereegranskat)abstract
- An ad hoc network can be set up by a number of units without the need of any permanent infrastructure. Two units establish a communication link if the channel quality is sufficiently high. As not all pairs of units can establish direct links, traffic between two units may have to be relayed through other units. This is known as the multi-hop functionality. In military command and control systems, ad hoc networks are also referred to as multi-hop radio networks. Spatial TDMA (STDMA) is a scheme for access control in ad hoc networks. STDMA improves TDMA by allowing simultaneous transmission of multiple units. In this paper, we study the optimization problem of STDMA scheduling, where the objective is to find minimum-length schedules. Previous work for this problem has focused on heuristics, whose performance is difficult to analyze when optimal solutions are not known. We develop novel mathematical programming formulations for this problem, and present a column generation solution method. Our numerical experiments show that the method generates a very tight bound to the optimal schedule length, and thereby enables optimal or near-optimal solutions. The column generation method can be used to provide benchmarks when evaluating STDMA scheduling algorithms. In particular, we use the bound obtained in the column generation method to evaluate a simple greedy algorithm that is suitable for distributed implementations.
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