A nasal injection of adiponectin: a novel therapeutic strategy against neurodegenerative disease

2015 Fiscal Year Final Research Report

• Project/Area Number: 25640030
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: HASHIMOTO Makoto 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., 副参事研究員 (50189502)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: αシヌクレイン / βシヌクレイン / パーキンソン病 / アルツハイマー病 / アディポネクチン

Outline of Final Research Achievements

Neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. To investigate possible roles of adiponectin (APN), the anti-diabetes protein, in the pathogenesis of α-synucleinopathies, we investigated autopsy brain of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and analyzed the effects of APN in cellular and in mouse models of α-synucleinopathies.In autopsy brains, APN was localized in Lewy bodies derived from PD and DLB. In neuronal cells expressing α-synuclein (αS), aggregation of αS was suppressed by treatment with recombinant APN in an AdipoRI-AMP kinase pathway-dependent manner. Concomitantly, phosphorylation and release of αS were significantly decreased by APN. In αS transgenic mice, both histopathology and movement disorder were significantly improved by intra nasal treatment with globular APN. Collectively, APN could possess a therapeutic potential against α-synucleinopathies.

Free Research Field

神経変性疾患