Journal ArticleDOI
Priorities in Parkinson's disease research
Wassilios G. Meissner,Wassilios G. Meissner,Mark Frasier,Thomas Gasser,Christopher G. Goetz,Andres M. Lozano,Paola Piccini,Jose A. Obeso,Olivier Rascol,Anthony H.V. Schapira,Valerie Voon,David M. Weiner,François Tison,François Tison,Erwan Bezard +14 more
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TLDR
This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address treatment goals of Parkinson's disease.Abstract:
The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.read more
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Journal ArticleDOI
An Essay on the Shaking Palsy
TL;DR: In this paper, the authors present a conciliatory explanation for the present publication, in which, it is acknowledged, that mere conjecture takes the place of experiment; and, that analogy is the substitute for anatomical examination, the only sure foundation for pathological knowledge.
Journal ArticleDOI
Adenosine receptors as drug targets — what are the challenges?
TL;DR: The biology of adenosine signalling is focused on to identify hurdles in the development of additional pharmacological compounds targeting adenoine receptors and discuss strategies to overcome these challenges.
Journal ArticleDOI
Chromone: A Valid Scaffold in Medicinal Chemistry
Alexandra Gaspar,Alexandra Gaspar,Maria João Matos,Maria João Matos,Jorge Garrido,Jorge Garrido,Eugenio Uriarte,Fernanda Borges +7 more
TL;DR: This work was supported by the Foundation for Science and Technology (FCT), Portugal (projects PTDC/QUI-QUI/113687/2009 and PEst-C/QUI/UI0081/2013) and SFRH/BD/61262/2009.
Journal ArticleDOI
Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations
Benjamin Dehay,Mathieu Bourdenx,Philippe Gorry,Serge Przedborski,Miquel Vila,Miquel Vila,Stéphane Hunot,Andrew B. Singleton,C. Warren Olanow,Kalpana M Merchant,Erwan Bezard,Gregory A. Petsko,Wassilios G. Meissner +12 more
TL;DR: This work critically assess the potential of experimental therapies targeting α-synuclein, and discusses steps that need to be taken for target validation and drug development.
Journal ArticleDOI
Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.
Matthieu F. Bastide,Wassilios G. Meissner,Barbara Picconi,Stefania Fasano,Pierre-Olivier Fernagut,Michael Feyder,Veronica Francardo,Cristina Alcacer,Yunmin Ding,Riccardo Brambilla,Gilberto Fisone,A. Jon Stoessl,Mathieu Bourdenx,Michel Engeln,Sylvia Navailles,Philippe De Deurwaerdère,Wai Kin D. Ko,Nicola Simola,Micaela Morelli,Laurent Groc,Maria Cruz Rodriguez,Eugenia V. Gurevich,Maryka Quik,Michele Morari,Manuela Mellone,Fabrizio Gardoni,Elisabetta Tronci,Dominique Guehl,François Tison,Alan R. Crossman,Un Jung Kang,Kathy Steece-Collier,Susan H. Fox,Manolo Carta,M. Angela Cenci,Erwan Bezard +35 more
TL;DR: The present review attempts to provide an overview of the current understanding of dyskinesia and other L-dopa-induced dysfunctions to help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.
References
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Journal ArticleDOI
SNCA Variants Are Associated with Increased Risk for Multiple System Atrophy
Sonja W. Scholz,Sonja W. Scholz,Henry Houlden,Claudia Schulte,Manu Sharma,Abi Li,Daniela Berg,Anna Melchers,Reema Paudel,J. Raphael Gibbs,J. Raphael Gibbs,Javier Simón-Sánchez,Coro Paisán-Ruiz,Jose Bras,Jinhui Ding,Honglei Chen,Bryan J. Traynor,Sampath Arepalli,Ryan R. Zonozi,Tamas Revesz,Janice L. Holton,Nicholas W. Wood,Andrew J. Lees,Wolfgang H. Oertel,Ullrich Wüllner,Stefano Goldwurm,Maria Teresa Pellecchia,Thomas Illig,Olaf Riess,Hubert H. Fernandez,Ramon L. Rodriguez,Michael S. Okun,Werner Poewe,Gregor K. Wenning,John Hardy,Andrew B. Singleton,Thomas Gasser +36 more
TL;DR: SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA and the 10 most significant SNPs were replicated in additional 108 MSA cases and 537 controls.
Journal ArticleDOI
Effects of expectation on placebo-induced dopamine release in Parkinson disease.
S. Lidstone,Michael Schulzer,Katherine Dinelle,Edwin Mak,Vesna Sossi,Thomas J. Ruth,Raúl de la Fuente-Fernández,Anthony G. Phillips,A. Jon Stoessl +8 more
TL;DR: The strength of belief of improvement can directly modulate dopamine release in patients with PD and the importance of uncertainty and/or salience over and above a patient's prior treatment response in regulating the placebo effect is demonstrated.
Journal ArticleDOI
Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.
Christopher G. Goetz,Philippe Damier,Christine Hicking,Eugene M. Laska,Thomas Müller,C. Warren Olanow,Olivier Rascol,Hermann Russ +7 more
TL;DR: Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia and future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome.
Journal ArticleDOI
Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis.
Herbert Y. Meltzer,Roger Mills,Stephen Revell,Hilde Williams,Ann Johnson,Daun Bahr,Joseph H. Friedman +6 more
TL;DR: Pimavanserin showed significantly greater improvement in psychosis in patients with PDP at a dose which did not impair motor function, or cause sedation or hypotension, which support the hypothesis that attenuation of psychosis secondary to DA receptor stimulation in PDP may be achieved through selective 5-HT2A receptor antagonism.
Journal ArticleDOI
Caffeine, postmenopausal estrogen, and risk of Parkinson's disease
Alberto Ascherio,Honglei Chen,Michael A. Schwarzschild,Shumin M. Zhang,Graham A. Colditz,Frank E. Speizer +5 more
TL;DR: Caffeine reduces the risk of PD among women who do not use postmenopausal hormones, but increases risk among hormone users, so clinical trials of caffeine or estrogens in women should avoid the combined use of these agents.
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