Journal ArticleDOI
Dopaminergic Loss and Inclusion Body Formation in α-Synuclein Mice: Implications for Neurodegenerative Disorders
Eliezer Masliah,Edward Rockenstein,Isaac Veinbergs,Margaret Mallory,Makoto Hashimoto,Ayako Takeda,Yutaka Sagara,Abbyann Sisk,Lennart Mucke +8 more
TLDR
Results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.Abstract:
To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.read more
Citations
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Protein Misfolding, Functional Amyloid, and Human Disease
TL;DR: The relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate is discussed and some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior is described.
Journal ArticleDOI
Parkinson's disease: Mechanisms and models
TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.
Journal ArticleDOI
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
TL;DR: It is reported that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity.
Journal ArticleDOI
The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.
Juan J. Zarranz,Javier Alegre,Juan Carlos Gómez-Esteban,Elena Lezcano,Raquel Ros,Israel Ampuero,Lídice Vidal,Janet Hoenicka,Olga Rodriguez,Begoña Atarés,Verónica Llorens,Estrella Gomez Tortosa,Teodoro del Ser,David G. Munoz,Justo García de Yébenes +14 more
TL;DR: Dementia with Lewy bodies is related to mutation of α‐synuclein, and the novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid in a much conserved area of the protein, is likely to produce severe disturbance of protein function.
Journal ArticleDOI
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.
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.
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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
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
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Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
Dora Games,David S. Adams,Ree Alessandrini,Robin Barbour,Patricia Borthelette,Catherine Blackwell,Tony Carr,J. C. Clemens,Thomas Donaldson,Frances Gillespie,Terry Guido,Stephanie Hagopian,Kelly Johnson-Wood,Karen Khan,Michael K. Lee,Paul Leibowitz,Ivan Lieberburg,Sheila P. Little,Eliezer Masliah,Lisa McConlogue,Martin Montoya-Zavala,Lennart Mucke,Lisa Paganini,Elizabeth Penniman,Michael Power,Dale Schenk,Peter Seubert,Ben W. Snyder,Ferdie Soriano,Hua Tan,James Vitale,Sam Wadsworth,Ben Wolozin,Jun Zhao +33 more
TL;DR: Transgenic mice that express high levels of human mutant APP support a primary role for APP/Aβ in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
Journal ArticleDOI
Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the hd mutation
Stephen W. Davies,Mark Turmaine,Barbara A. Cozens,Marian DiFiglia,Alan H. Sharp,Christopher A. Ross,Eberhard Scherzinger,Erich E. Wanker,Laura Mangiarini,Gillian P. Bates +9 more
TL;DR: In this paper, the authors observed that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to 157 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype.
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