However, several studies suggest that endogenous ligands, such as heparan sulfate, heat shock proteins, and high-mobility group box 1 (HMGB1) can stimulate TLR signaling suggesting a role for sterile inflammation in diseases like synucleinopathies, which have the hallmark feature of increased amounts of misfolded endogenous proteins (Yu et al., 2010). Here, HMGB1 is linked to synucleinopathy.