Therapeutic potential of the anti-neurodegeneration effect of benign adipokines

2016 Fiscal Year Final Research Report

• Project/Area Number: 25290019
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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)
• Co-Investigator(Kenkyū-buntansha): 小柳 清光 信州大学, 医学部, 教授 (00134958)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: アディポネクチン / 神経変性疾患 / パーキンソン病 / αシヌクレイン / アルツハイマー病

Outline of Final Research Achievements

Growing evidence suggests that neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. We investigated autopsy brain of α-synucleinopathies including Parkinson's disease and dementia with Lewy bodies, and analyzed the effects of adiponectin (APN) in cellular and in mouse models of α-synucleinopathies.
We observed that APN is localized in Lewy bodies derived from the brains of α-synucleinopathies. 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 transgenic mice expressing αS, both histopathology and movement disorder were improved by intranasal treatment with globular APN.
Taken together, APN may suppress neurodegeneration through modification of the metabolic pathway in α-synucleinopathies.

Free Research Field

神経変性疾患