High-mobility group protein b1 (HMGB1) is a ubiquitous nuclear protein that is released extracellularly after cell activation, stress, injury, or apoptosis and plays an important role in neurodegenerative diseases by mediating neuroinflammation [99, 100]; an in vivo trial demonstrated that [101] that inhibition of HMGB1 may alleviate NLRP3 inflammatory vesicle-mediated inflammatory responses in hippocampal neurons via the TLR4/MAPKs/NF-κB signaling pathway. Here, HMGB1 is linked to neurodegenerative disease.