Therapeutic approaches to target alpha-synuclein pathology
TLDR
It is concluded that alpha-synuclein remains one of the most compelling therapeutic targets for Parkinson's disease, and related synucleinopathies, and that the multitude of approaches being tested provides hope for the future.About:
This article is published in Experimental Neurology.The article was published on 2017-12-01 and is currently open access. It has received 170 citations till now. The article focuses on the topics: Synucleinopathies.read more
Citations
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Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations
Anthony E. Lang,Alberto J. Espay +1 more
TL;DR: It is unknown whether the dysfunctional molecular pathways/organelles amenable to modification occur in a sequential fashion across most clinically affected individuals or manifest differentially in independent molecular subtypes of PD.
Journal ArticleDOI
Dementia with Lewy bodies and Parkinson’s disease-dementia: current concepts and controversies
TL;DR: Both DLB and PDD show heterogeneous pathology and neurochemistry, suggesting that they share important common underlying molecular pathogenesis with AD and other proteinopathies, and there remains a pressing need to differentiate them more clearly.
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The vermiform appendix impacts the risk of developing Parkinson’s disease
Bryan A. Killinger,Zachary Madaj,Jacek Sikora,Nolwen L. Rey,Nolwen L. Rey,Alec J. Haas,Yamini Vepa,Daniel Lindqvist,Honglei Chen,Paul M. Thomas,Patrik Brundin,Lena Brundin,Viviane Labrie,Viviane Labrie +13 more
TL;DR: It is proposed that the normal human appendix contains pathogenic forms of α-synuclein that affect the risk of developing Parkinson’s disease.
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α-Synuclein misfolding and aggregation: Implications in Parkinson's disease pathogenesis.
TL;DR: The structural and functional aspects of α-Syn and role of potential factors that may contribute to the underlying mechanism of synucleinopathies are focused on to identify novel targets and develop specific therapeutic strategies to combat Parkinson's and other protein aggregation related neurodegenerative diseases.
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Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic
TL;DR: This review focuses on therapeutic paradigms that are under clinical development and highlights a wide range of key outstanding questions in PD.
References
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Journal ArticleDOI
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Mike A. Nalls,Nathan Pankratz,Christina M. Lill,Chuong B. Do,Dena G. Hernandez,Dena G. Hernandez,Mohamad Saad,Mohamad Saad,Mohamad Saad,Anita L. DeStefano,Anita L. DeStefano,Eleanna Kara,Jose Bras,Manu Sharma,Claudia Schulte,Margaux F. Keller,Sampath Arepalli,Christopher Letson,Connor Edsall,Hreinn Stefansson,Xinmin Liu,Hannah A. Pliner,Joseph H. Lee,Rong Cheng,M. Arfan Ikram,John P. A. Ioannidis,Georgios M. Hadjigeorgiou,Joshua C. Bis,Maria Martinez,Maria Martinez,Joel S. Perlmutter,Alison Goate,Karen Marder,Brian K. Fiske,Margaret Sutherland,Georgia Xiromerisiou,Richard H. Myers,Lorraine N. Clark,Kari Stefansson,John Hardy,Peter Heutink,Honglei Chen,Nicholas W. Wood,Henry Houlden,Haydeh Payami,Alexis Brice,Alexis Brice,William K. Scott,Thomas Gasser,Lars Bertram,Nicholas Eriksson,Tatiana Foroud,Andrew B. Singleton +52 more
TL;DR: This article conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls.
Journal ArticleDOI
Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease
Ellen Sidransky,Mike A. Nalls,Jan O. Aasly,Judith Aharon-Peretz,Grazia Annesi,Egberto Reis Barbosa,Anat Bar-Shira,Daniela Berg,Jose Bras,Jose Bras,Alexis Brice,Alexis Brice,Chiung-Mei Chen,Lorraine N. Clark,Christel Condroyer,Elvira Valeria De Marco,Alexandra Durr,Alexandra Durr,Michael J. Eblan,Stanley Fahn,Matthew J. Farrer,Hon-Chung Fung,Ziv Gan-Or,Thomas Gasser,Ruth Gershoni-Baruch,Ruth Gershoni-Baruch,Nir Giladi,Nir Giladi,Alida Griffith,Tanya Gurevich,Tanya Gurevich,Cristina Januário,Peter Kropp,Anthony E. Lang,Guey Jen Lee-Chen,Suzanne Lesage,Karen Marder,Ignacio F. Mata,Anat Mirelman,Jun Mitsui,Ikuko Mizuta,Giuseppe Nicoletti,Giuseppe Nicoletti,Catarina R. Oliveira,Ruth Ottman,Avi Orr-Urtreger,Lygia da Veiga Pereira,Aldo Quattrone,Aldo Quattrone,Ekaterina Rogaeva,Arndt Rolfs,Hanna Rosenbaum,Roberto Rozenberg,Ali Samii,Ali Samii,Ali Samii,Ted Samaddar,Claudia Schulte,Manu Sharma,Manu Sharma,Andrew B. Singleton,Andrew B. Singleton,Mariana Spitz,Mariana Spitz,Eng-King Tan,Eng-King Tan,Nahid Tayebi,Tatsushi Toda,André R. Troiano,Shoji Tsuji,Matthias Wittstock,Tyra G. Wolfsberg,Yih-Ru Wu,Cyrus P. Zabetian,Yi Zhao,Shira G. Ziegler +75 more
TL;DR: Data collected demonstrate that there is a strong association between GBA mutations and Parkinson's disease, and those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were morelikely to have atypical clinical manifestations.
Journal ArticleDOI
The many faces of α-synuclein: from structure and toxicity to therapeutic target
TL;DR: An overview of current knowledge and prevailing hypotheses regarding the conformational, oligomerization and aggregation states of α-syn and their role in regulating α- synuclein function in health and disease is provided.
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α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation
TL;DR: It is proposed that destabilization of the helically folded tetramer precedes α-synuclein misfolding and aggregation in Parkinson’s disease and other human synucleinopathies, and that small molecules that stabilize the physiological tetramer could reduce α- Synuclein pathogenicity.
Journal ArticleDOI
Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein
TL;DR: It is shown that trehalose also protects cells against subsequent pro-apoptotic insults via the mitochondrial pathway, which may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.
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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