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
Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations.
Zejuan Sheng,Shuo Zhang,Daisy Bustos,Tracy Kleinheinz,Claire E. Le Pichon,Sara L. Dominguez,Hilda Solanoy,Jason Drummond,Xiaolin Zhang,Xiao Ding,Fang Cai,Qinghua Song,Xianting Li,Zhenyu Yue,Marcel P. van der Brug,Daniel J. Burdick,Janet Gunzner-Toste,Huifen Chen,Xingrong Liu,Anthony A. Estrada,Zachary Kevin Sweeney,Kimberly Scearce-Levie,John Moffat,Donald S. Kirkpatrick,Haitao Zhu +24 more
TL;DR: It is demonstrated that LRRK2 autophosphorylation on Ser1292 occurs in vivo and is enhanced by several familial PD mutations including N1437H, R1441G/C, G2019S, and I2020T, which may contribute to the cellular effects of certain PD mutations.
Journal ArticleDOI
A Progressive Mouse Model of Parkinson’s Disease: The Thy1-aSyn (“Line 61”) Mice
Marie-Françoise Chesselet,Franziska Richter,Chunni Zhu,Iddo Magen,Melanie B. Watson,Sudhakar R. Subramaniam +5 more
TL;DR: This work extensively characterized a mouse model over-expressing full-length, human, wild-type alpha-synuclein under the Thy-1 promoter, which reproduces many features of sporadic PD and provides an opportunity to test novel neuroprotective strategies during different phases of the disorder using endpoint measures with high power to detect drug effects.
Journal ArticleDOI
α-Synuclein–Induced Down-Regulation of Nurr1 Disrupts GDNF Signaling in Nigral Dopamine Neurons
Mickael Decressac,Banafsheh Kadkhodaei,Bengt Mattsson,Ariadna Laguna,Thomas Perlmann,Thomas Perlmann,Anders Björklund +6 more
TL;DR: It is shown that the intracellular response to GDNF is blocked in DA neurons that overexpress α-synuclein, and that Ret expression was also reduced in nigral DA neurons in PD patients, suggesting Nurr1 is a key player in the cellular defense against α- synuclein toxicity.
Journal ArticleDOI
Nicotine as a potential neuroprotective agent for Parkinson's disease.
TL;DR: Findings suggest that nicotine and nAChR drugs represent promising therapeutic agents for the management of Parkinson's disease.
Journal ArticleDOI
Integrating Pathways of Parkinson's Disease in a Molecular Interaction Map
Kazuhiro Fujita,Marek Ostaszewski,Yukiko Matsuoka,Samik Ghosh,Enrico Glaab,Christophe Trefois,Isaac Crespo,Thanneer M. Perumal,Wiktor Jurkowski,Paul Antony,Nico J. Diederich,Nico J. Diederich,Manuel Buttini,Akihiko Kodama,Venkata P. Satagopam,Serge Eifes,Antonio del Sol,Reinhard Schneider,Hiroaki Kitano,Rudi Balling +19 more
TL;DR: A computationally tractable, comprehensive molecular interaction map of Parkinson's disease that integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation is introduced.
References
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Journal ArticleDOI
Parkinson’s disease: clinical features and diagnosis
TL;DR: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease and genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.
Journal ArticleDOI
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium
Ian G. McKeith,Ian G. McKeith,Dennis W. Dickson,James Lowe,Murat Emre,John T. O'Brien,Howard Feldman,Jeffrey L. Cummings,John E. Duda,Carol F. Lippa,Elaine K. Perry,Dag Aarsland,Hiroyuki Arai,Clive Ballard,B. F. Boeve,David J. Burn,Durval C. Costa,T. Del Ser,Bruno Dubois,Douglas Galasko,Serge Gauthier,Christopher G. Goetz,Estrella Gómez-Tortosa,Glenda M. Halliday,L. A. Hansen,John Hardy,Takeshi Iwatsubo,Raj N. Kalaria,Daniel I. Kaufer,Rose Anne Kenny,Amos D. Korczyn,Kenji Kosaka,Virginia M.-Y. Lee,Andrew J. Lees,Irene Litvan,Elisabet Londos,Oscar L. Lopez,Satoshi Minoshima,Yoshikuni Mizuno,José Antonio Molina,Elizabeta B. Mukaetova-Ladinska,Florence Pasquier,Robert H. Perry,Jörg B. Schulz,John Q. Trojanowski,Masahito Yamada +45 more
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Journal ArticleDOI
α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew B. Singleton,Matthew J. Farrer,Joshua C. Johnson,Amanda Singleton,Stephen Hague,Jennifer M. Kachergus,Mary M. Hulihan,Terhi Peuralinna,Amalia Dutra,Robert L. Nussbaum,Sarah Lincoln,Anthony Crawley,Melissa Hanson,Demetrius M. Maraganore,Charles H. Adler,Mark R. Cookson,Manfred D. Muenter,Melisa J. Baptista,David Miller,J. Blancato,John Hardy,Katrina Gwinn-Hardy +21 more
TL;DR: In this article, the α-synuclein was identified as the major component of Lewy bodies, the pathological hallmark of Parkinson's disease, and of glial cell cytoplasmic inclusions.
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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