C9orf72 and amyotrophic lateral sclerosis: In C9ORF72-ALS, both poly(PR) and poly(GR) are toxic in vitro and in vivo.9,10,16,37 Both poly(PR) and poly(GR) contain 50% arginine, and the positive charge of arginine allows them to interact with acidic macromolecules, including nucleic acids and proteins, resulting in neurotoxicity.