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These results point out that the robustness of the protein homeostasis system depends on the absence of proteins highly weak to aggregation upon any type of stress and on the presence of modifications in aggregation state of regulatory mechanisms that restore protein solubility upon specific perturbations.

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Huntington’s disease mutations lead to expansion of a polyglutamine (polyQ) sequence in Httex1 to lengths longer than 36Q, whereas the wild-sort protein is often lower than 25Q ( Duyao et al., 1993 ). PolyQ-growth causes Httex1 to become highly aggregation susceptible, which manifests as intracellular inclusion bodies as the disease progresses ( Davies et al., 1997 ; DiFiglia et al., 1997 ; Scherzinger et al., 1997 ). We and others have used transient expression constructs of Httex1 fused to fluorescent proteins as fashions for replicating important features of the illness, including protein homeostasis stress ( Arrasate et al., 2004 ; Hosp et al., 2017 ; Kim et al., 2016 ; Moily et al., 2017 ; Ramdzan et al., 2017 ). Mutant Httex1-fluorescent protein constructs progressively form massive cytosolic inclusions in cell culture over time.

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