PMID: 32532315Dec 3, 2018Paper

GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

Translational Neurodegeneration
William R SwindellDorothy Ko

Abstract

Amyotrophic lateral sclerosis (ALS) is currently an incurable disease without highly effective pharmacological treatments. The peptide drug GM604 (GM6 or Alirinetide) was developed as a candidate ALS therapy, which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic profile. GM6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways, but mechanisms of action are not fully understood. This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment (6, 24 and 48 h). We identified 2867 protein-coding genes with expression significantly altered by GM6 (FDR < 0.10). Early (6 h) responses included up-regulation of Notch and hedgehog signaling components, with increased expression of developmental genes mediating neurogenesis and axon growth. Prolonged GM6 treatment (24 and 48 h) altered the expression of genes contributing to cell adhesion and the extracellular matrix. GM6 further down-regulated the expression of genes associated with mitochondria, inflammatory responses, mRNA processing and chromatin organization. GM6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger...Continue Reading

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Citations

May 24, 2019·Journal of Translational Medicine·William R SwindellJohn J Kopchick
Feb 25, 2019·Molecular Neurobiology·Jin YuMark S Kindy
Jul 8, 2020·Biomolecules·Jose L SalazarShinya Yamamoto
Jul 2, 2021·Frontiers in Molecular Biosciences·Walter CabriAlessandra Tolomelli
Jan 6, 2022·Journal of Medicinal Chemistry·Olmo Martín-CámaraJ Carlos Menéndez

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