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Parkinson's Disease and Related Disorders

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

アラキドン酸は FABP-3 を介してαーシヌクレインの凝集を促進する
Arachidonic acid promotes α-synuclein toxicity through FABP-3 in the dopaminergic neurons

  • P1-303
  • 福永 浩司 / Kohji Fukunaga:1 塩田 倫史 / Norifumi Shioda:1 大和田 祐二 / Yuji Owada:2 
  • 1:東北大学大学院薬学研究科薬理学分野 / Dept Pharmacol, Grad Sch of Pharm Scis, Tohoku Univ, Sendai Japan 2:山口大学大学院医学研究科器官解剖学分野 / Dept Organ Anat, Grad Sch Med Yamaguchi Univ, Ube Japan 

[Background] Fatty acid-binding protein 3 (FABP3) is highly expressed in the dopaminergic neurons, especially in the substantia nigra pars compacta (SNpc) (Shioda et al., J Neurosci, 2010;30:3146-55). FABP3 null mice exhibit hypo-dopaminergic phenotype in the extrapyramidal symptom. Notably, α-synuclein oligomerization is critical to the pathogenesis of Parkinson's disease (PD) and is regulated by long-chain polyunsaturated fatty acids (LCPUFAs) such as arachidonic acid (AA) and docosahexaenoic acid (DHA). We have recently hypothesized that FABP3 triggers α-synuclein oligomerization in the dopaminergic neurons and AA promotes α-synuclein oligomerization in dopaminergic neurons. [Methods] MPTP-induced α-synuclein oligomerization was assessed in wild and FABP3 null mice. In vitro studies using PC12 cells evaluated the promotion of α-synuclein oligomerization by AA treatment through FABP-3. [Results] MPTP-induced α-synuclein oligomerization in the SNpc was attenuated in the FABP3 null mice compared to wild mice. Immunohistochemical analyses revealed that MPTP-induced α-synuclein accumulation in the SNpc was also attenuated in FABP3 null mice. In vitro study using PC12 cells confirmed that α-synuclein oligomerization with FABP3 was promoted by AA (100µM) treatment. [Conclusion] Taken together, AA is risk factor for the formation of α-synuclein oligomerization through FABP-3 in the dopaminergic neurons of PD patients. The evidences also propose a novel therapeutic strategy for PD. [Acknowledgements] This work was supported by KAKENHI 25293124 and 24102505 (KF).

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