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A Peptidylic Inhibitor for Neutralizing (GGGGCC)-Associated Neurodegeneration in C9ALS-FTD.

Mol Ther Nucleic Acids. 2019-06; 
ZhangQian,AnYing,ChenZhefan Stephen,KoonAlex Chun,LauKwok-Fai,NgoJacky Chi Ki,ChanHo Yin E
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Peptide Synthesis All peptides were purchased from GenScript. The sequences of TAT peptide, TAT-RRM1-P1, TAT-RRM2-P1 (TAT-BIND), TATRRM3-P1, and TAT-RRM4-P1, are shown in Table 1. Get A Quote

摘要

One drug, two diseases is a rare and economical therapeutic strategy that is highly desirable in the pharmaceutical industry. We previously reported a 21-amino acid peptide named beta-structured inhibitor for neurodegenerative diseases (BIND) that can effectively inhibit expanded CAG trinucleotide toxicity in polyglutamine (polyQ) diseases. Here we report that BIND also effectively inhibits GGGGCC repeat-mediated neurodegeneration in vitro and in vivo. When fused with a cell-penetrating peptide derived from the transactivator of transcription (TAT) protein of the HIV, TAT-BIND reduces cell death, formation of GGGGCC RNA foci, and levels of poly-GR, poly-GA, and poly-GP dipeptide proteins in cell m... More

关键词

C9ORF72,G4C2,amyotrophic lateral sclerosis,cell-penetrating peptide,frontotemporal dementia,peptide inhib
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