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Unbiased Screens for Modifiers of Alpha-Synuclein Toxicity.
Höllerhage, Matthias; Bickle, Marc; Höglinger, Günter U.
Afiliación
  • Höllerhage M; Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 81377, Munich, Germany.
  • Bickle M; Department of Neurology, Technical University of Munich (TUM), 81675, Munich, Germany.
  • Höglinger GU; HT-Technology Development Studio, Max Planck Institute of Molecular Cell Biology and Genetics, 01307, Dresden, Germany.
Curr Neurol Neurosci Rep ; 19(2): 8, 2019 02 09.
Article en En | MEDLINE | ID: mdl-30739256
PURPOSE OF REVIEW: We provide an overview about unbiased screens to identify modifiers of alpha-synuclein (αSyn)-induced toxicity, present the models and the libraries that have been used for screening, and describe how hits from primary screens were selected and validated. RECENT FINDINGS: Screens can be classified as either genetic or chemical compound modifier screens, but a few screens do not fit this classification. Most screens addressing αSyn-induced toxicity, including genome-wide overexpressing and deletion, were performed in yeast. More recently, newer methods such as CRISPR-Cas9 became available and were used for screening purposes. Paradoxically, given that αSyn-induced toxicity plays a role in neurological diseases, there is a shortage of human cell-based models for screening. Moreover, most screens used mutant or fluorescently tagged forms of αSyn and only very few screens investigated wild-type αSyn. Particularly, no genome-wide αSyn toxicity screen in human dopaminergic neurons has been published so far. Most unbiased screens for modifiers of αSyn toxicity were performed in yeast, and there is a lack of screens performed in human and particularly dopaminergic cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alfa-Sinucleína Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Curr Neurol Neurosci Rep Asunto de la revista: NEUROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alfa-Sinucleína Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Curr Neurol Neurosci Rep Asunto de la revista: NEUROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos