In the context of neurodegenerative diseases, where a sterile inflammation occurs [16], different endogenous disease-related ligands may bind to and activate TLRs, such as amyloid β (Aβ) [21], α-synuclein (α-syn) [22], high-mobility group box protein 1 (HMGB1) [23], galectin-3 (GAL3; coded by Lgals3) [24,25], etc. After ligand recognition, TLRs assemble and activate different downstream signaling pathways, which activate several immune responses. Here, LGALS3 is linked to neurodegenerative disease.