Both Familial Parkinson’s Disease Mutations Accelerate α-Synuclein Aggregation
Linda O. Narhi,Stephen J. Wood,Shirley Steavenson,Yijia Jiang,Dan Anafi,Stephen Kaufman,Francis Hall Martin,Karen C. Sitney,Paul Denis,Jean-Claude Louis,Jette Wypych,Anja Leona Biere,Martin Citron +12 more
TLDR
It is shown that both wild type and mutant α-synuclein form insoluble fibrillar aggregates with antiparallel β-sheet structure upon incubation at physiological temperature in vitro, and that aggregate formation is accelerated by both PD-linked mutations.About:
This article is published in Journal of Biological Chemistry.The article was published on 1999-04-02 and is currently open access. It has received 722 citations till now. The article focuses on the topics: Wild type & Mutant protein.read more
Citations
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Interleukin-1 polymorphisms associated with increased risk of gastric cancer
Emad M. El-Omar,Emad M. El-Omar,Mary Carrington,Wong Ho Chow,Kenneth E.L. McColl,Jay H. Bream,Howard A. Young,Jesus Herrera,Jolanta Lissowska,Chiu Chin Yuan,Nathaniel Rothman,George Lanyon,Maureen P. Martin,Joseph F. Fraumeni,Charles S. Rabkin +14 more
TL;DR: It is reported that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleucine-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer.
Journal ArticleDOI
A Drosophila model of Parkinson's disease
Mel B. Feany,Welcome Bender +1 more
TL;DR: The Drosophila model recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease.
Journal ArticleDOI
Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders.
Byron Caughey,Peter T. Lansbury +1 more
TL;DR: Recent biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibril form that is typically observed at autopsy may actually be neuroprotective.
Journal ArticleDOI
Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: Implications for pathogenesis and therapy
Kelly A. Conway,Seung Jae Lee,Jean-Christophe Rochet,Tomas T. Ding,Robin E. Williamson,Peter T. Lansbury +5 more
TL;DR: In this in vitro study, drug candidates that inhibit alpha-synuclein fibrillization but do not block its oligomerization could mimic the A30P mutation and thus may accelerate disease progression.
Journal ArticleDOI
Alpha-synuclein and neurodegenerative diseases
TL;DR: The molecular properties of the synucleins, the different diseases characterized by the accumulation of α-synuclein, and the possible mechanisms by which dysfunction ofα- synuclein might lead to neurodegeneration are reviewed.
References
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Journal ArticleDOI
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
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Alpha-synuclein in Lewy bodies.
Maria Grazia Spillantini,Marie L. Schmidt,Virginia M.-Y. Lee,John Q. Trojanowski,Ross Jakes,Michel Goedert +5 more
TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
Journal ArticleDOI
Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation
David L. Lacey,Emma Timms,Hong-Lin Tan,Michael J. Kelley,Colin R. Dunstan,Tim Burgess,Robin Elliott,Anne Colombero,Gary Elliott,S. Scully,Hailing Hsu,John K. Sullivan,Nessa Hawkins,E. Davy,C. Capparelli,Alana Eli,Yi-xin Qian,Steve Kaufman,Ildiko Sarosi,Victoria Shalhoub,Giorgio Senaldi,Jane Guo,John M. Delaney,William J. Boyle +23 more
TL;DR: The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGl and OPG are key extracellular regulators of osteoclast development.
Journal ArticleDOI
Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
Rejko Krüger,Wilfried Kuhn,Thomas Müller,Dirk Woitalla,Manuel B. Graeber,Sigfried Kösel,Horst Przuntek,Jörg T. Epplen,Ludger Schöls,Olaf Riess +9 more
Journal ArticleDOI
α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies
TL;DR: It is shown thatLewy bodies and Lewy neurites from Parkinson’s disease and dementia with Lewy bodies are stained strongly by antibodies directed against amino- terminal and carboxyl-terminal sequences of α-synuclein, showing the presence of full- length or close to full-length α- synuclein.
Related Papers (5)
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