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, α-synuclein aggregation, and mitochondrial dysfunction may contribute to PD onset; however, the molecular mechanisms underlying these pathophysiological processes are still under elucidation. Interestingly, recent evidence has indicated that High-mobility group box 1 (HMGB1), a DNA-binding protein that can be actively secreted by inflammatory cells and passively released by necrotic cells may play a key role in PD pathogenesis. HMGB1 has been shown to participate in neuroinflammation, modulate autophagy and apoptosis as well as regulate gene transcription. Furthermore, therapeutic targeting of HMGB1 with either anti-HMGB1 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 of HMGB1 in PD pathogenesis and discusses potential therapeutic approaches.
Keywords: PD; RAGE; HMGB1; autophagy; neurodegeneration; neuroinflammation.
© 2018 International Society for Neurochemistry.