High‐mobility group box 1 in Parkinson's disease: from pathogenesis to therapeutic approaches

摘要

Abstract Parkinson's disease (PD ) presents the second most common neurodegenerative disorder with largely unknown pathogenesis and inefficient therapeutic management. Accumulating data indicate that neuroinflammation, autophagy impairment, ?synuclein aggregation, and mitochondrial dysfunction may contribute toPD onset; however, the molecular mechanisms underlying these pathophysiological processes are still under elucidation. Interestingly, recent evidence has indicated that Highmobility group box 1 (HMGB 1), aDNA binding protein that can be actively secreted by inflammatory cells and passively released by necrotic cells may play a key role inPD pathogenesis.HMGB 1 has been shown to participate in neuroinflammation, modulate autophagy and apoptosis as well as regulate gene transcription. Furthermore, therapeutic targeting ofHMGB 1 with either antiHMGB 1 antibodies or selective inhibitors, such as glycyrrhizin, has been shown to inhibit neurodegeneration in animal models. This review provides an update of recent data on the emerging role ofHMGB 1 inPD pathogenesis and discusses potential therapeutic approaches.