High‐mobility group box 1 in Parkinson's disease: from pathogenesis to therapeutic approaches. Issue 3 (3rd July 2018) - Angelopoulou, Efthalia
Abstract : 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, 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. Abstract : Recent evidence implicates High‐mobility group box 1 (HMGB1) protein in Parkinson's disease pathogenesis with potential for therapeutic targeting. HMGB1 is implicated in neuroinflammation via macrophage antigen complex 1 (Mac1)‐HMGB1 interaction that activates nuclear factor‐κΒ (NF‐κB) and nicotinamide adenine dinucleotide phosphate (NADPH), inducing tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (IL‐1β), and nitric oxide (NO) production. It is also involved in neurodegeneration processes via Mac1‐HMGB1 interaction and blood–brain barrier (BBB) disruption. HMGB1 regulates autophagy, mitochondrial function, α‐synuclein (SNCA) gene transcription, and tyrosine hydroxylase (TH) expression via Receptor for Advanced Glycated End products (RAGE)‐HMGB1 interaction and c‐Jun N‐terminal kinase (JNK) activation.