Connexin astrocytopathy in the pathogenesis of demyelination in concentric sclerosis and multiple sclerosis

连接蛋白星形细胞病在同心硬化症和多发性硬化症脱髓鞘发病机制中的作用

• 批准号: 23659459
• 负责人: KIRA Jun-ichi
• 金额: $ 2.33万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659459/
• 关键词: コネキシン; 多発性硬化症; 視神経脊髄炎; Balo 病; Balo病; アクアポリン４; グリア間相互作用; アストロサイトパチー

To investigate the relationship between astrocytopathy and demyelination, we examined the expression of connexins (Cx). We pathologically evaluated the expressions of astrocytic Cx43/Cx30 and oligodendroglial Cx47/Cx32 among autopsied cases with demyelinating disorders. In Balo’ s disease (BD), Cx43, Cx32 and Cx47 were extensively diminished. In the leading edge of Balo’s lesions, Cx43 and AQP4 loss preceded Cx47 loss. Three cases with multiple sclerosis (MS) and six with neuromyelitis optica (NMO) showed preferential Cx43 and AQP4 loss far beyond the demyelinated areas, while vasculocentric deposition of immunoglobulins or complements was observed in four of the six NMO cases. Some NMO cases showed preferential myelin-associated glycoprotein (MAG) loss in AQP4- and Cx43-diminished active lesions. Our findings indicate that disruption of Cx gap junction and preferential MAG loss could occur in MS, BD and NMO, and could be a common denominator. Inhibition of Cx hemichannels is a possible therapeutic target for demyelinating disorders

为了研究星形胶质细胞病和脱髓鞘病之间的关系，我们对脱髓鞘病（BD）尸检病例中星形胶质细胞 Cx43/Cx30 和少突胶质细胞 Cx47/Cx32 的表达进行了病理学评估。 Cx43、Cx32 和 Cx47 的领先优势大幅减弱。 Balo 病变中，Cx43 和 AQP4 缺失先于 Cx47 缺失，3 例多发性硬化症 (MS) 病例和 6 例视神经脊髓炎 (NMO) 病例显示，Cx43 和 AQP4 优先缺失，远远超出脱髓鞘区域，而 4 例中观察到免疫球蛋白或补体以血管为中心的沉积。 6 例 NMO 病例中，一些 NMO 病例表现出髓鞘相关糖蛋白（MAG）优先丢失。我们的研究结果表明，MS、BD 和 NMO 中可能发生 Cx 间隙连接的破坏和优先的 MAG 丢失，并且抑制 Cx 半通道可能是脱髓鞘疾病的一个可能的治疗靶点。

项目成果

Impaired cytoplastic-nuclear transport of hypoxia-inducible factor-1αin amgotrophic lateral sclerosis.

肌萎缩侧索硬化症中缺氧诱导因子 1α 的细胞质-核转运受损。

• DOI: 10.1111/bpa.12040
• 发表时间: 2013
• 影响因子: 6.4
• 作者: Kira J et al

Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and .negative Sjogren's syndrome patients with central nervous system manifestations

抗水通道蛋白4抗体阳性和阴性干燥综合征患者中枢神经系统表现的临床、免疫学和神经影像学特征比较

• 发表时间: 2012
• 影响因子: 5.8
• 作者: Riwanti Estiasari; Matsushita T; Masaki K; Akiyama T; Yonekawa T; Isobe N; Kira J
• 通讯作者: Kira J

Intramuscular interferon bata-la is effective in Japanese patients with relapsiny-remittingz multiple sclerosis: a pre-treatment versus treatment comparison study of gadolinium-enhanced MRI brain lesions

肌内注射干扰素 bata-la 对日本复发缓解型多发性硬化症患者有效：钆增强 MRI 脑损伤的治疗前与治疗比较研究

• 发表时间: 2012
• 影响因子: 5.8
• 作者: Saida T; Itoyama Y; Tashiro K; Kira J; Hao Q; the Interferon Beta
• 通讯作者: the Interferon Beta

Clinical disability progression and platelet GP IIb/IIIa values in patients with atopic myelitis

特应性脊髓炎患者的临床残疾进展和血小板 GP IIb/IIIa 值

• 发表时间: 2012
• 影响因子: 3.3
• 作者: Gulibahaer A; Yamashita K; Torii T ; Furuta K; Isobe N; Matsushita T; Masaki K; Matsumoto S; Kira J
• 通讯作者: Kira J

Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and –negative Sjögren’s syndrome patients with central nervous system manifestations.

抗水通道蛋白4抗体阳性和阴性干燥综合征患者中枢神经系统表现的临床、免疫学和神经影像学特征比较。

• 发表时间: 2012
• 作者: Kira J et al