start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=2650 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Mobility Group Box-1 and Blood-Brain Barrier Disruption en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption. en-copyright= kn-copyright= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=high mobility group box-1 kn-keyword=high mobility group box-1 en-keyword=blood-brain barrier kn-keyword=blood-brain barrier en-keyword=inflammation kn-keyword=inflammation en-keyword=stroke kn-keyword=stroke en-keyword=trauma kn-keyword=trauma en-keyword=vascular endothelial cell kn-keyword=vascular endothelial cell en-keyword=pericyte kn-keyword=pericyte en-keyword=monoclonal antibody kn-keyword=monoclonal antibody END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=2623 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuron-Astrocyte Interactions in Parkinson's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=astrocyte kn-keyword=astrocyte en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=dopaminergic neuron kn-keyword=dopaminergic neuron en-keyword=neuroinflammation kn-keyword=neuroinflammation en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=alpha-synuclein kn-keyword=alpha-synuclein en-keyword=mitochondria kn-keyword=mitochondria END