Development of autophagy enhancing chemicals based on Parkinson's disease pathogenesis.

2017 Fiscal Year Final Research Report

• Project Area: Multidisciplinary research on autophagy: from molecular mechanisms to disease states
• Project/Area Number: 25111007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Juntendo University
• Principal Investigator: SAIKI Shinji 順天堂大学, 医学部, 准教授 (00339996)
• Co-Investigator(Kenkyū-buntansha): 佐藤 栄人 順天堂大学, 医学部, 准教授 (00445537)
• Co-Investigator(Renkei-kenkyūsha): IMOTO Masaya 慶應義塾大学, 理工学部, 教授 (60213253) ; HATTORI Nobutaka 順天堂大学, 医学部, 教授 (80218510)
• Research Collaborator: FUNAYAMA Manabu 順天堂大学, 医学部, 准教授 (70468578) ; ISHIKAWA Kei-ichi 順天堂大学, 医学部, 非常勤助教 (90733973) ; FURUYA Norihiko 順天堂大学, 医学部, 助教 (50401188) ; SASAZAWA Yukiko 日本学術振興会, 特別研究員(RPD) (20594922) ; YAMADA Daisuke 順天堂大学, 医学部, 助教 (30757539)
• Project Period (FY): 2013-06-28 – 2018-03-31
• Keywords: オートファジー / 神経内科学 / ケミカルバイオロジー

Outline of Final Research Achievements

According to mutation screening of the WDR45 gene responsible for SENDA, we identified high prevalence of the disease in patients with characteristic phenotype.
We revealed that Dynactin mutant, with pathogenic mutant of Perry syndrome, one of the parkinsonian disorders, has inhibiting effect on autophagic flux by decreased autophagosome-lysosome fusion step, resulting in apoptosis. Also, CHCHD2, a novel gene responsible for autosomal dominant Parkinson's disease, was identified and now its molecular function is investigated within the mitochondria. Using TH neurons selective autophagy deficient mice, intraneuronal inclusions have been detected in the affected lesions.

Free Research Field

神経内科学