Fig. 4

Genetic Background Affects the Protein Folding Environment. a Age of Huntington’s Disease onset as a function of polyQ repeat length (adapted from Wexler, et. al., (2004) Proc. Natl., Acad. Sci.). b Schematic representation of the decline in proteostasis buffering capacity as the misfolded protein load increases. Three sources of misfolded protein are considered, including destabilizing polymorphisms in the genetic background (red), disease-associate proteins (brown), and sporadic mutation to DNA or accumulated damage during aging (blue). Symptoms associated with neurodegenerative disease or aging are more likely to be observed when the misfolded protein load is sufficiently high (shaded in pink) as compared to normal (green) or intermediate levels (yellow) of misfolding