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Parkinson's Disease and Related Disorders

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Adiponectin potentiates insulin signaling and ameliorates α-synuclein pathology in a rat neuroblastoma cell line

  • P3-289
  • 関山 一成 / Kazunari Sekiyama:1 高松 芳樹 / Yoshiki Takamatsu:1 橋本 款 / Makoto Hashimoto:1 
  • 1:都医学研・運動・感覚システム・パーキンソン病 / Div Sensory and Motor Systems, Tokyo Metro Inst Med Sci, Tokyo, Japan 

Recent study suggests that lifestyle-related disorders, such as type II diabetes, may increase the risk of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease (PD). However, the mechanisms are obscure. Since adiponectin (APN), a well-known anti-diabetic adipokine, has been shown to play beneficial roles in various tissues and organs, we wondered if APN is protective against neurodegenerative disorders, including α-synucleinopathies. We further speculated that decrease of APN under the diabetic condition, might lead to increased risk of neurodegenerative disorders. If this is the case, reinforcement of APN might be useful for the therapeutic strategy aganst PD and related α-synucleinopathies. Consistent with this view, we found that treatment of recombinant APN protein in the α-synucleinopathies models, including rat B103 neurobalstoma cells expressing human α-synuclein (hαS) and transgenic mouse expressing hαS, was effective to ameliorate neurodegeneration in both experimental models (Sekiyama et al, submitted).
As a next step, the present study was carried out to better understand the mechanisms by which APN protects against α-synucleinopathies. We predicted one possible mechanism that APN may sensitize insulin signaling pathway, potentiating anti-neurodegenerative effects of endogenous insulin. Supporting our hypothesis, B103 rat neuroblstoma cells expressing hαS pretreated with APN protein, exhibited increased levels of insulin-stimulated phosphorylation of IRS and AKT, both of which are well-characterized as molecules situated in the insulin receptor signaling pathway. Furthermore, evaluation of the combined effect of insulin plus APN is now in progress using the hαS transgenic mice. Collectively, these results suggest that APN positively regulates through insulin signaling pathway and might be useful for the therapeutic purpose of PD and related α-synucleinopathies

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