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
Citations
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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
Rivastigmine for Dementia Associated with Parkinson's Disease
Murat Emre,Dag Aarsland,Alberto Albanese,E. J. Byrne,Günther Deuschl,P.P. De Deyn,Franck Durif,Jaime Kulisevsky,T. van Laar,Alan Lees,Werner Poewe,A Robillard,MM Rosa,Erik Ch. Wolters,P Quarg,Sibel Tekin,Roger Lane +16 more
TL;DR: In this paper, the effects of the dual cholinesterase inhibitor rivastigmine in patients with mild-to-moderate dementia associated with Parkinson's disease were investigated.
Journal ArticleDOI
Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial.
Michael G. Kaplitt,Andrew Feigin,Andrew Feigin,Chengke Tang,Helen L. Fitzsimons,Paul J. Mattis,P. Lawlor,Ross J. Bland,Deborah Young,Kristin Strybing,David Eidelberg,David Eidelberg,Matthew J. During,Matthew J. During +13 more
TL;DR: AAV-GAD gene therapy of the subthalamic nucleus is safe and well tolerated by patients with advanced Parkinson's disease, suggesting that in-vivo gene therapy in the adult brain might be safe for various neurodegenerative diseases.
Journal ArticleDOI
Sydney multicenter study of Parkinson's disease: Non-L-dopa–responsive problems dominate at 15 years
TL;DR: It is concluded that the most disabling long‐term problems of Parkinson's disease relate to the emergence of symptoms that are not improved by L‐dopa, and neuroprotective interventions in Parkinson’s disease should be judged by their ability to improve non‐L‐Dopa–responsive aspects of the disease.
Journal ArticleDOI
In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
Alexander Gerhard,Nicola Pavese,Gary Hotton,Federico Turkheimer,Meltem Es,Alexander Hammers,Karla Eggert,Wolfgang H. Oertel,Richard B. Banati,Richard B. Banati,David J. Brooks +10 more
TL;DR: In vivo findings confirm that widespread microglial activation is associated with the pathological process in PD and suggest that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.
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Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more