The H50Q mutation induces a 10-fold decrease in the solubility of α-synuclein.
Riccardo Porcari,Christos Proukakis,Christopher A. Waudby,Benedetta Bolognesi,Palma Mangione,Jack F. S. Paton,Stephen Mullin,Lisa D. Cabrita,Amanda Penco,Annalisa Relini,Guglielmo Verona,Michele Vendruscolo,Monica Stoppini,Gian Gaetano Tartaglia,Carlo Camilloni,John Christodoulou,Anthony H.V. Schapira,Vittorio Bellotti +17 more
TL;DR: The finding that wild-type α-synuclein can decelerate the aggregation kinetics of the H50Q variant in a dose-dependent manner when coaggregating with it suggests that the precise balance of α- synuclein synthesized from the wild- type and mutant alleles may influence the natural history and heterogeneous clinical phenotype of Parkinson disease.
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About: This article is published in Journal of Biological Chemistry. The article was published on 23 Jan 2015. and is currently open access. The article focuses on the topics: Protein aggregation.
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Citations
Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease.
TL;DR: Evidence for the neuropathological role for α-synuclein in the dysfunction of dopamine neurons in PD is discussed and insights into the structure, localization, and cellular roles forα- synuclein that may influence its aggregation properties, ultimately impacting its pathogenicity, role in lysosomal dysfunction and activation of the neuroimmune response are discussed.
634
Cellular and Molecular Basis of Neurodegeneration in Parkinson Disease.
TL;DR: The mutations of main seven genes linked to Parkinson disease are summarized, the potential mechanisms for the loss of dopaminergic neurons are discussed, the development direction for treatment of PD is expected, and the findings from scientists are conducive to understand the pathological mechanisms.
Structures of fibrils formed by α-synuclein hereditary disease mutant H50Q reveal new polymorphs
TL;DR: Cryo-EM analyses of α-synuclein fibrils formed with hereditary Parkinson's disease mutant H50Q reveal features that help explain the mutant’s properties in vitro and in cells.
α-Synuclein in Parkinson's disease: causal or bystander?
Peter Riederer,Peter Riederer,Daniela Berg,Nicolas Casadei,Fubo Cheng,Joseph Classen,Christian Dresel,Wolfgang H. Jost,Rejko Krüger,Thomas Müller,Heinz Reichmann,Olaf Rieß,Alexander Storch,Sabrina Strobel,Thilo van Eimeren,Hans-Ullrich Völker,Jürgen Winkler,Konstanze F. Winklhofer,Ullrich Wüllner,Friederike Zunke,Camelia-Maria Monoranu +20 more
TL;DR: While rare SNCA gene mutations are causal for a minority of familial PD patients, in sporadic PD (where common S NCA polymorphisms are the most consistent genetic risk factor across populations worldwide, accounting for 95% of PD patients) α-syn pathology is an important feature.
110
Targeting disordered proteins with small molecules using entropy
TL;DR: It is discussed quite generally how an overall decrease in the free energy associated with intermolecular binding can originate from different combinations of enthalpic and entropic contributions.
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References
NMRPipe: a multidimensional spectral processing system based on UNIX pipes
TL;DR: The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.
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Mutation in the α-synuclein gene identified in families with Parkinson's disease
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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.
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.
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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