Systems Medicine of Mitochondrial Parkinson’s Disease

Project Information

SysMedPD

Grant agreement ID: 668738

DOI

10.3030/668738

Project closed

EC signature date 1 December 2015

Start date 1 December 2015

End date 30 November 2020

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 5 999 990,00

EU contribution

€ 5 999 990,00

Coordinated by

UNIVERSITEIT LEIDEN
Netherlands

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Demonstrators, pilots, prototypes (5)

Miniaturised metabolomics platform including storage device for sample transport
Computational model of brain metabolism

Computational model of brain metabolism (lead partner: UL-Fleming)

Complete mitochondrial molecular network reconstruction

Complete mitochondrial molecular network reconstruction (lead partner: UL-Balling)

Metabolomics platform for mitochondrial dysfunction
Draft mitochondrial molecular network reconstruction

Draft mitochondrial molecular network reconstruction (lead partner: UL-Balling)

Documents, reports (4)

Successful differentiation of dopaminergic neurons from iPSCs and subsequent transplantation into NOD SCID mice

Successful differentiation of dopaminergic neurons from iPSCs and subsequent transplantation into NOD SCID mice (lead partner: UL-Schwamborn)

Successful neurochemical analysis performed in transplanted SCID mice and correlation to phenotype progression investigated
Open access summary report
Characterisation of in vivo amperometric sensors and microdialysis in the striatum of mice

Other (1)

SysMedPD audio-visual material

Websites, patent fillings, videos etc. (1)

External project website

Publications

Peer reviewed articles (28)

Passive controlled flow for Parkinson's disease neuronal cell culture in 3D microfluidic devices

Author(s): Javier Jarazo; Khalid I. W. Kane; Ronan M. T. Fleming; Ronan M. T. Fleming; Jens Christian Schwamborn; Edinson Lucumi Moreno
Published in: Organs-on-a-Chip, Issue 2, 2020, ISSN 2666-1020
Publisher: Elsevier
DOI: 10.1016/j.ooc.2020.100005

Personalized whole‐body models integrate metabolism, physiology, and the gut microbiome

Author(s): Ines Thiele, Swagatika Sahoo, Almut Heinken, Johannes Hertel, Laurent Heirendt, Maike K Aurich, Ronan MT Fleming
Published in: Molecular Systems Biology, Issue 16/5, 2020, ISSN 1744-4292
Publisher: Nature Publishing Group
DOI: 10.15252/msb.20198982

Mitochondrial damage-associated inflammation highlights biomarkers in PRKN/PINK1 parkinsonism

Author(s): Max Borsche, Inke R König, Sylvie Delcambre, Simona Petrucci, Alexander Balck, Norbert Brüggemann, Alexander Zimprich, Kobi Wasner, Sandro L Pereira, Micol Avenali, Christian Deuschle, Katja Badanjak, Jenny Ghelfi, Thomas Gasser, Meike Kasten, Philip Rosenstiel, Katja Lohmann, Kathrin Brockmann, Enza Maria Valente, Richard J Youle, Anne Grünewald, Christine Klein
Published in: Brain, Issue 143, 2020, Page(s) 3041-3051, ISSN 0006-8950
Publisher: Oxford University Press
DOI: 10.1093/brain/awaa246

Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects

Author(s): Max Borsche, Sandro L. Pereira, Christine Klein, Anne Grünewald
Published in: Journal of Parkinson's Disease, Issue 11/1, 2021, Page(s) 45-60, ISSN 1877-7171
Publisher: IOS Press
DOI: 10.3233/jpd-201981

Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy

Author(s): Vasudev Kantae, Elke H. J. Krekels, Michiel J. Van Esdonk, Peter Lindenburg, Amy C. Harms, Catherijne A. J. Knibbe, Piet H. Van der Graaf, Thomas Hankemeier
Published in: Metabolomics, Issue 13/1, 2017, ISSN 1573-3882
Publisher: Springer Verlag
DOI: 10.1007/s11306-016-1143-1

MetaboTools: A Comprehensive Toolbox for Analysis of Genome-Scale Metabolic Models

Author(s): Maike K. Aurich, Ronan M. T. Fleming, Ines Thiele
Published in: Frontiers in Physiology, Issue 7, 2016, ISSN 1664-042X
Publisher: Frontiers Research Foundation
DOI: 10.3389/fphys.2016.00327

High-throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform

Author(s): Nienke R. Wevers, Remko van Vught, Karlijn J. Wilschut, Arnaud Nicolas, Chiwan Chiang, Henriette L. Lanz, Sebastiaan J. Trietsch, Jos Joore, Paul Vulto
Published in: Scientific Reports, Issue 6/1, 2016, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/srep38856

Real-Time Amperometric Recording of Extracellular H2O2 in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study

Author(s): Caroline H. Reid, Niall J. Finnerty
Published in: Sensors, Issue 17/7, 2017, Page(s) 1596, ISSN 1424-8220
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/s17071596

Embryonic development of selectively vulnerable neurons in Parkinson’s disease

Author(s): Miguel A. P. Oliveira, Rudi Balling, Marten P. Smidt, Ronan M. T. Fleming
Published in: npj Parkinson's Disease, Issue 3/1, 2017, ISSN 2373-8057
Publisher: Nature publishing group
DOI: 10.1038/s41531-017-0022-4

96 perfusable blood vessels to study vascular permeability in vitro

Author(s): V. van Duinen, A. van den Heuvel, S. J. Trietsch, H. L. Lanz, J. M van Gils, A. J. van Zonneveld, P. Vulto, T. Hankemeier
Published in: Scientific Reports, Issue 7/1, 2017, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-017-14716-y

Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0

Author(s): Laurent Heirendt, Sylvain Arreckx, Thomas Pfau, Sebastián N. Mendoza, Anne Richelle, Almut Heinken, Hulda S. Haraldsdóttir, Jacek Wachowiak, Sarah M. Keating, Vanja Vlasov, Stefania Magnusdóttir, Chiam Yu Ng, German Preciat, Alise Žagare, Siu H. J. Chan, Maike K. Aurich, Catherine M. Clancy, Jennifer Modamio, John T. Sauls, Alberto Noronha, Aarash Bordbar, Benjamin Cousins, Diana C. El Assal,
Published in: Nature Protocols, Issue 14/3, 2019, Page(s) 639-702, ISSN 1754-2189
Publisher: Nature Publishing Group
DOI: 10.1038/s41596-018-0098-2

3D Cultures of Parkinson's Disease-Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing

Author(s): Silvia Bolognin, Marie Fossépré, Xiaobing Qing, Javier Jarazo, Janez Ščančar, Edinson Lucumi Moreno, Sarah L. Nickels, Kobi Wasner, Nassima Ouzren, Jonas Walter, Anne Grünewald, Enrico Glaab, Luis Salamanca, Ronan M. T. Fleming, Paul M. A. Antony, Jens C. Schwamborn
Published in: Advanced Science, Issue 6/1, 2019, Page(s) 1800927, ISSN 2198-3844
Publisher: Wiley
DOI: 10.1002/advs.201800927

FACS-Assisted CRISPR-Cas9 Genome Editing Facilitates Parkinson's Disease Modeling

Author(s): Jonathan Arias-Fuenzalida, Javier Jarazo, Xiaobing Qing, Jonas Walter, Gemma Gomez-Giro, Sarah Louise Nickels, Holm Zaehres, Hans Robert Schöler, Jens Christian Schwamborn
Published in: Stem Cell Reports, Issue 9/5, 2017, Page(s) 1423-1431, ISSN 2213-6711
Publisher: Cell Press
DOI: 10.1016/j.stemcr.2017.08.026

Comparative evaluation of atom mapping algorithms for balanced metabolic reactions: application to Recon 3D

Author(s): German A. Preciat Gonzalez, Lemmer R. P. El Assal, Alberto Noronha, Ines Thiele, Hulda S. Haraldsdóttir, Ronan M. T. Fleming
Published in: Journal of Cheminformatics, Issue 9/1, 2017, ISSN 1758-2946
Publisher: Chemistry Central
DOI: 10.1186/s13321-017-0223-1

Parkinson’s Disease-Associated Mutant LRRK2-Mediated Inhibition of miRNA Activity is Antagonized by TRIM32

Author(s): Laura Gonzalez-Cano, Ingeborg Menzl, Johan Tisserand, Sarah Nicklas, Jens C. Schwamborn
Published in: Molecular Neurobiology, Issue 55/4, 2018, Page(s) 3490-3498, ISSN 0893-7648
Publisher: Humana Press, Inc.
DOI: 10.1007/s12035-017-0570-y

ReconMap: an interactive visualization of human metabolism

Author(s): Alberto Noronha, Anna Dröfn Daníelsdóttir, Piotr Gawron, Freyr Jóhannsson, Soffía Jónsdóttir, Sindri Jarlsson, Jón Pétur Gunnarsson, Sigurður Brynjólfsson, Reinhard Schneider, Ines Thiele, Ronan M. T. Fleming
Published in: Bioinformatics, 2017, Page(s) btw667, ISSN 1367-4803
Publisher: Oxford University Press
DOI: 10.1093/bioinformatics/btw667

Guidelines for Fluorescent Guided Biallelic HDR Targeting Selection With PiggyBac System Removal for Gene Editing

Author(s): Javier Jarazo, Xiaobing Qing, Jens C. Schwamborn
Published in: Frontiers in Genetics, Issue 10, 2019, ISSN 1664-8021
Publisher: Frontiers Media
DOI: 10.3389/fgene.2019.00190

Automated microfluidic cell culture of stem cell derived dopaminergic neurons

Author(s): Khalid I. W. Kane, Edinson Lucumi Moreno, Siham Hachi, Moriz Walter, Javier Jarazo, Miguel A. P. Oliveira, Thomas Hankemeier, Paul Vulto, Jens C. Schwamborn, Martin Thoma, Ronan M. T. Fleming
Published in: Scientific Reports, Issue 9/1, 2019, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-018-34828-3

Modeling Parkinson’s disease in midbrain-like organoids

Author(s): Lisa M. Smits, Lydia Reinhardt, Peter Reinhardt, Michael Glatza, Anna S. Monzel, Nancy Stanslowsky, Marcelo D. Rosato-Siri, Alessandra Zanon, Paul M. Antony, Jessica Bellmann, Sarah M. Nicklas, Kathrin Hemmer, Xiaobing Qing, Emanuel Berger, Norman Kalmbach, Marc Ehrlich, Silvia Bolognin, Andrew A. Hicks, Florian Wegner, Jared L. Sterneckert, Jens C. Schwamborn
Published in: npj Parkinson's Disease, Issue 5/1, 2019, ISSN 2373-8057
Publisher: Nature Research
DOI: 10.1038/s41531-019-0078-4

LC–MS/MS analysis of the central energy and carbon metabolites in biological samples following derivatization by dimethylaminophenacyl bromide

Author(s): Cornelius C.W. Willacey, Martijn Naaktgeboren, Edinson Lucumi Moreno, Agnieszka B. Wegrzyn, Daan van der Es, Naama Karu, Ronan M.T. Fleming, Amy C. Harms, Thomas Hankemeier
Published in: Journal of Chromatography A, Issue 1608, 2019, Page(s) 460413, ISSN 0021-9673
Publisher: Elsevier BV
DOI: 10.1016/j.chroma.2019.460413

Chaperone-mediated autophagy as a therapeutic target for Parkinson disease

Author(s): Philip Campbell, Huw Morris, Anthony Schapira
Published in: Expert Opinion on Therapeutic Targets, Issue 22/10, 2018, Page(s) 823-832, ISSN 1472-8222
Publisher: Ashley Publications Ltd.
DOI: 10.1080/14728222.2018.1517156

Impaired serine metabolism complements LRRK2-G2019S pathogenicity in PD patients

Author(s): Sarah Louise Nickels, Jonas Walter, Silvia Bolognin, Deborah Gérard, Christian Jaeger, Xiaobing Qing, Johan Tisserand, Javier Jarazo, Kathrin Hemmer, Amy Harms, Rashi Halder, Philippe Lucarelli, Emanuel Berger, Paul M.A. Antony, Enrico Glaab, Thomas Hankemeier, Christine Klein, Thomas Sauter, Lasse Sinkkonen, Jens Christian Schwamborn
Published in: Parkinsonism & Related Disorders, Issue 67, 2019, Page(s) 48-55, ISSN 1353-8020
Publisher: Elsevier BV
DOI: 10.1016/j.parkreldis.2019.09.018

An electrochemical investigation into the effects of local and systemic administrations of sodium nitroprusside in brain extracellular fluid of mice

Author(s): Caroline H. Reid, Niall J. Finnerty
Published in: Bioelectrochemistry, Issue 132, 2020, Page(s) 107441, ISSN 1567-5394
Publisher: Elsevier BV
DOI: 10.1016/j.bioelechem.2019.107441

Recon3D enables a three-dimensional view of gene variation in human metabolism

Author(s): Elizabeth Brunk, Swagatika Sahoo, Daniel C Zielinski, Ali Altunkaya, Andreas Dräger, Nathan Mih, Francesco Gatto, Avlant Nilsson, German Andres Preciat Gonzalez, Maike Kathrin Aurich, Andreas Prlić, Anand Sastry, Anna D Danielsdottir, Almut Heinken, Alberto Noronha, Peter W Rose, Stephen K Burley, Ronan M T Fleming, Jens Nielsen, Ines Thiele, Bernhard O Palsson
Published in: Nature Biotechnology, Issue 36/3, 2018, Page(s) 272-281, ISSN 1087-0156
Publisher: Nature Publishing Group
DOI: 10.1038/nbt.4072

Long Term Amperometric Recordings in the Brain Extracellular Fluid of Freely Moving Immunocompromised NOD SCID Mice

Author(s): Caroline Reid, Niall Finnerty
Published in: Sensors, Issue 17/3, 2017, Page(s) 419, ISSN 1424-8220
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/s17020419

Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells

Author(s): Anna S. Monzel, Lisa M. Smits, Kathrin Hemmer, Siham Hachi, Edinson Lucumi Moreno, Thea van Wuellen, Javier Jarazo, Jonas Walter, Inga Brüggemann, Ibrahim Boussaad, Emanuel Berger, Ronan M.T. Fleming, Silvia Bolognin, Jens C. Schwamborn
Published in: Stem Cell Reports, Issue 8/5, 2017, Page(s) 1144-1154, ISSN 2213-6711
Publisher: Cell Press
DOI: 10.1016/j.stemcr.2017.03.010

Mechanism of action and potential applications of selective inhibition of microsomal prostaglandin E synthase-1-mediated PGE2 biosynthesis by sonlicromanol’s metabolite KH176m

Author(s): X. Jiang, H. Renkema, B. Pennings, S. Pecheritsyna, J. C. Schoeman, T. Hankemeier, J. Smeitink, J. Beyrath
Published in: Scientific Reports, Issue 11/1, 2021, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-79466-w

Parkin Deficiency Appears Not to Be Associated with Cardiac Damage in Parkinson's Disease

Author(s): Michaela Trilck‐Winkler, Max Borsche, Inke R. König, Alexander Balck, Insa Lenz, Meike Kasten, Katja Lohmann, Kathrin Brockmann, Enza Maria Valente, Christine Klein, Norbert Brüggemann, Philip Seibler
Published in: Movement Disorders, Issue 36/1, 2021, Page(s) 271-273, ISSN 0885-3185
Publisher: John Wiley & Sons Inc.
DOI: 10.1002/mds.28422

Thesis and dissertations (3)

Selective vulnerability in Parkinson's disease: contributions from neuronal connectivity, lineage and functional identity

Author(s): Oliveira, Miguel
Published in: 2017
Publisher: University of Luxembourg

The Parkinson’s Disease Associated Pink1-Parkin Pathway In Pathology And Development

Author(s): Jarazo, Javier
Published in: 2018
Publisher: University of Luxembourg

Neurochemical Monitoring in a Humanised Murine Model of Parkinson's disease using Amperometry and Microdialysis

Author(s): Caroline Reid
Published in: 2019
Publisher: Maynooth University

Other (3)

In Vivo Phenotyping Of Parkinson-Specific Stem Cells Reveals Increased a-Synuclein Levels But No Spreading

Author(s): Schwamborn, Jens; Hemmer, Kathrin; Smits, Lisa; Bolognin, Silvia
Published in: 2017
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/140178

Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids

Author(s): Lisa M. Smits, Stefano Magni, Kamil Grzyb, Paul MA. Antony, Rejko Krüger, Alexander Skupin, Silvia Bolognin, Jens C. Schwamborn
Published in: 2019
Publisher: Bioarxiv
DOI: 10.1101/589598

Parkinson’s disease phenotypes in patient specific brain organoids are improved by HP-β-CD treatment.

Author(s): Javier Jarazo, Kyriaki Barmpa, Isabel Rosety, Lisa M. Smits, Jonathan Arias-Fuenzalida, Jonas Walter, Gemma Gomez-Giro, Anna S. Monzel, Xiaobing Qing, Gerald Cruciani, Ibrahim Boussaad, Christian Jäger, Aleksandar Rakovic, Emanuel Berger, Silvia Bolognin, Paul M. A. Antony, Christine Klein, Rejko Krüger, Philip Seibler, Jens C. Schwamborn
Published in: 2019
Publisher: Bioarxiv
DOI: 10.1101/813089

Non-peer reviewed articles (1)

Neural Stem Cells of Parkinson's Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality

Author(s): Jonas Walter, Silvia Bolognin, Paul M.A. Antony, Sarah L. Nickels, Suresh K. Poovathingal, Luis Salamanca, Stefano Magni, Rita Perfeito, Fredrik Hoel, Xiaobing Qing, Javier Jarazo, Jonathan Arias-Fuenzalida, Tomasz Ignac, Anna S. Monzel, Laura Gonzalez-Cano, Luis Pereira de Almeida, Alexander Skupin, Karl J. Tronstad, Jens C. Schwamborn
Published in: Stem Cell Reports, Issue 12/5, 2019, Page(s) 878-889, ISSN 2213-6711
Publisher: Cell Press
DOI: 10.1016/j.stemcr.2019.03.004