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Parkinson's Disease and Related Disorders

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Involvement of HDAC10 in MPP+- treated neuronal cell death and in brains with Parkinson's disease

  • P3-294
  • 永野 義人 / Yoshito Nagano:1 倉重 毅志 / Takashi Kurashige:1 土肥 栄祐 / Eisuke Dohi:1 宍戸 丈郎 / Takeo Shishido:1 高橋 哲也 / Tetsuya Takahashi:1 丸山 博文 / Hirofumi Maruyama:1 松本 昌泰 / Masayasu Matsumoto:1 
  • 1:広島大学大学院医歯薬保健学研究院 脳神経内科学 / Dept Clinical Neuroscience and Therapeutics, Hiroshima Univ, Hiroshima, Japan 

Parkinson's disease (PD) is characterized by the progressive loss of nigrostriatal dopamine neurons and the formation of pathological hallmark, Lewy body. Impairment of autophagy has been shown to result in protein aggregation, leading to Lewy body formation. Recent paper showed that histone deacetylase (HDAC)10 promoted autophagy-mediated cell survival and protected cancer cells from cytotoxic agents. However, the function of HDAC10 in neurodegenerative diseases remains unclear. In the present study, pathological studies showed that HDAC10 localized in the halo part of Lewy body in PD brains. Immunofluorescence studies showed that HDAC10 was clearly colocalized with α-synuclein which is the main component of Lewy body. We also checked that the protein expression levels of HDAC10 in PD patient's brain and control brains by western blotting. The result suggested that the expression levels of HDAC10 in PD brains are significantly higher than those of control brains. Furthermore, we found that knockdown of HDAC10 using siRNA enhanced neuronal cell death compared to control cells after MPP+ treatment. Interestingly, the number of cells containing protein aggregates were increased in HDAC10 knockdown cells compared to normal control cells, suggesting that HDAC10 could be involved in the clearance of protein aggregates via autophagy. Taken together, HDAC10 would play an important role in Lewy body formation and neuronal cell survival in PD brains by mediating autophagy pathway.

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