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Loss of RAD-23 Protects Against Models of Motor Neuron Disease by Enhancing Mutant Protein Clearance.

Angela M JablonskiTodd LamitinaNicole F LiachkoMariangela SabatellaJiayin LuLei ZhangLyle W OstrowPreetika GuptaChia-Yen WuShachee DoshiJelena Mojsilovic-PetrovicHannes LansJiou WangBrian KraemerRobert G Kalb
Published in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
In this work, we identify RAD-23, a component of the protein homeostasis network and nucleotide excision repair pathway, as a modifier of the toxicity of two disease-causing, misfolding-prone proteins, SOD1 and TDP-43. Reducing the abundance of RAD-23 accelerates the degradation of mutant SOD1 and TDP-43 and reduces the cellular content of the toxic species. The existence of endogenous proteins that act as "anti-chaperones" uncovers new and general targets for therapeutic intervention.
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