Interface of neural activity, immunity and metabolism in acute encephalopathy

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04872
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: MIZUGUCHI Masashi 東京大学, 大学院医学系研究科(医学部), 教授 (20209753)
• Co-Investigator(Kenkyū-buntansha): 高梨 潤一 東京女子医科大学, 医学部, 教授 (00302555) ; 齋藤 真木子 東京大学, 医学部附属病院, 特任助教 (20225733)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 急性脳症 / 急性壊死性脳症 / けいれん重積型（二相性）急性脳症 / イオンチャネル / 自然免疫 / ミトコンドリア

Outline of Final Research Achievements

To explore abnormal intracellular signal transduction in acute encephalopathy including acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), we conducted gene and functional analyses of factors associated with the crosstalk between neural activity, immunity and metabolism. We identified cytokine and HLA polymorphisms as genetic predisposition in Japanese patients with sporadic ANE. We elucidated the association of RANBP2, the causative gene of familial ANE in Caucasians, with mitochondrial metabolism. We identified a polymorphism of CTLA4, a suppressor of innate immunity, as a risk factor for AESD. We also found the association of mutations of sodium channels, SCN1A and SCN2A, with multiple syndromes, and that of thermolabile variation of a mitochondrial enzyme, CPT2, with overall acute encephalopathy.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

急性脳症の多因子疾患としての本質が解明され、免疫、神経、代謝の全てが関連する複雑な病態の理解が進んだ。遺伝的背景の解明により、急性脳症の遺伝相談の道が開かれるとともに、自然免疫、神経興奮、エネルギー代謝に関わる新しい治療の標的分子が見つかった。