Physiological actions and pathological relevance of growth factors in the brain

2015 Fiscal Year Final Research Report

• Project/Area Number: 23228004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: The University of Tokyo
• Principal Investigator: NISHIHARA Masugi 東京大学, 農学生命科学研究科, 教授 (90145673)
• Co-Investigator(Kenkyū-buntansha): HASEGAWA Masato 公益財団法人東京都医学総合研究所, 認知症高次脳機能研究分野, 分野長 (10251232) ; NEDACHI Taku 東洋大学, 生命科学部, 教授 (50375200)
• Co-Investigator(Renkei-kenkyūsha): YAMANOUCHI Keitaro 東京大学, 大学院農学生命科学研究科, 准教授 (70272440) ; NAKAYAMA Hiroyuki 東京大学, 大学院農学生命科学研究科, 教授 (40155891) ; MATSUWAKI Takashi 東京大学, 大学院農学生命科学研究科, 助教 (20447361)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 脳・神経 / 成長因子 / 神経変性 / 神経新生

Outline of Final Research Achievements

The present study aims to elucidate the molecular mechanisms by which growth factors such as progranulin regulate neurodegeneration by combining physiological studies on the role of growth factors in modulating proliferation, differentiation and cell death of neurons and neuropathological studies on neurodegenerative diseases due to mutations in growth factor genes. The present study revealed that the expression of progranulin is increased by brain injury and stresses, and then progranulin is conveyed to lysosomes thereby decreasing lysosomal biogenesis, neuroinflammation and neuronal damages. In addition, the present study also suggests that lysosomal dysfunction with aging is exacerbated by progranulin deficiency, which leads the accumulation of abnormal protein with a resultant onset of neurodegenerative diseases.

Free Research Field

農学