blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and alzheimers disease缝隙连接的封锁hemichannel抑制疾病进展的肌萎缩性脊髓侧索硬化症小鼠模型和阿尔茨海默氏症.pdfVIP

Blockade of Gap Junction Hemichannel Suppresses Disease Progression in Mouse Models of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease 1 2 1 1 1 1 Hideyuki Takeuchi *, Hiroyuki Mizoguchi , Yukiko Doi , Shijie Jin , Mariko Noda , Jianfeng Liang , Hua 1 1 2 1 1 1 1 Li , Yan Zhou , Rarami Mori , Satoko Yasuoka , Endong Li , Bijay Parajuli , Jun Kawanokuchi , 1 2 3 4 1 1 Yoshifumi Sonobe , Jun Sato , Koji Yamanaka , Gen Sobue , Tetsuya Mizuno , Akio Suzumura 1 Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan, 2 Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan, 3 Laboratory for Motor Neuron Disease, RIKEN Brain Science Institute, Hirosawa, Wako, Saitama, Japan, 4 Department of Neurology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, Japan Abstract Background: Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer’s disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and