Relevance of high-mobility group protein box 1 to neurodegeneration

High-mobility group protein box 1 (HMGB1), also know as amphoterin, is a nonhistone nuclear protein with well-established functions in gene transcription and homeostasis regulation into the cell nucleus. Interestingly, the protein can be passively released in the extracellular space during necrosis, whereas retained into the nucleus by cells undergoing apoptosis. Also, immune cells actively release HMGB1 on stimulation. Emerging evidence undoubtedly demonstrates that extracellular HMGB1 engages membrane receptors on different cells signaling proliferation, differentiation, cytoprotection, as well as immune activation. Consistently, numerous reports point to HMGB1 as a novel player in disease pathogenesis in peripheral organs. This chapter provides an appraisal of the emerging roles of HMGB1 in neuropathology and the neuroinflammatory response, highlighting the relevance of HMGB1-blocking agents as innovative therapeutic tools to be harnessed for neuroprotection.