Glycine-alanine dipeptide repeat protein contributes to toxicity in a zebrafish model of C9orf72 associated neurodegeneration

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• 作者：Yu Ohki ; Andrea Wenninger-Weinzierl ; Alexander Hruscha…
• 关键词：Zebrafish ; C9orf72 ; poly ; GA toxicity
• 刊名：Molecular Neurodegeneration
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：12
• 期：1
• 全文大小：1504KB
• 刊物主题：Neurosciences; Neurology; Molecular Medicine;
• 出版者：BioMed Central
• ISSN：1750-1326
• 卷排序：12

文摘

BackgroundThe most frequent genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the expansion of a GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 (C9orf72) locus. The pathological hallmarks observed in C9orf72 repeat expansion carriers are the formation of RNA foci and deposition of dipeptide repeat (DPR) proteins derived from repeat associated non-ATG (RAN) translation. Currently, it is unclear whether formation of RNA foci, DPR translation products, or partial loss of C9orf72 predominantly drive neurotoxicity in vivo. By using a transgenic approach in zebrafish we address if the most frequently found DPR in human ALS/FTLD brain, the poly-Gly-Ala (poly-GA) protein, is toxic in vivo.