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
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TLDR
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.Abstract:
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. 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. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.read more
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Autophagic failure promotes the exocytosis and intercellular transfer of α-synuclein
TL;DR: It is suggested that the inefficient clearance of α-synuclein aggregates, which can be caused by reduced autophagic activity, leads to elevated α- synuclein exocytosis, thereby promoting α- Synuclein deposition and cell death in neighboring neurons.
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α-Synuclein Interacts with Glucocerebrosidase Providing a Molecular Link between Parkinson and Gaucher Diseases
Thai Leong Yap,James M. Gruschus,Arash Velayati,Wendy Westbroek,Ehud Goldin,Nima Moaven,Ellen Sidransky,Jennifer C. Lee +7 more
TL;DR: It is suggested that the α-syn-GCase association is favored in the lysosome, and that this noncovalent interaction provides the groundwork to explore molecular mechanisms linking PD with mutant GBA alleles.
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Tau Oligomers Impair Artificial Membrane Integrity and Cellular Viability
Katharina Flach,Isabel Hilbrich,Andrea Schiffmann,Ulrich Gärtner,Martin Krüger,Marion Leonhardt,Hanka Waschipky,Lukas Y. Wick,Thomas Arendt,Max Holzer +9 more
TL;DR: The findings suggest that oligomeric Tau aggregation intermediates are the most toxic compounds of Tau fibrillogenesis, which effectively decrease cell viability and increase phospholipid vesicle leakage.
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Parkinson's Disease-associated α-Synuclein Is More Fibrillogenic than β- and γ-Synuclein and Cannot Cross-seed Its Homologs
Anja Leona Biere,Stephen J. Wood,Jette Wypych,Shirley Steavenson,Yijia Jiang,Dan Anafi,Frederick W. Jacobsen,Mark A. Jarosinski,Gay-May Wu,Jean-Claude Louis,Francis Hall Martin,Linda O. Narhi,Martin Citron +12 more
TL;DR: β- and γ-synuclein are intrinsically less fibrillogenic than α- Synuclein and cannot form mixed fibrils with α- synuclein, which may explain why they do not appear in the pathological hallmarks of PD, although they are closely related to α-syn nuclein and are also abundant in brain.
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PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson’s disease rat model
Masatoshi Inden,Takahiro Taira,Yoshihisa Kitamura,Takashi Yanagida,Daiju Tsuchiya,Kazuyuki Takata,Daijiro Yanagisawa,Kaneyasu Nishimura,Takashi Taniguchi,Yoshiaki Kiso,Kanji Yoshimoto,Tomohiro Agatsuma,Shizuyo Koide-Yoshida,Shizuyo Koide-Yoshida,Sanae M.M. Iguchi-Ariga,Shun Shimohama,Hiroyoshi Ariga +16 more
TL;DR: Findings suggest that DJ-1 is a therapeutic target for Parkinson's disease, as production of reactive oxygen species and cell death induced by 6-OHDA in SH-SY5Y cells and mesencephalic neurons were inhibited by addition of the recombinantDJ-1.
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