Annals of Clinical Neurophysiology

The Korean Society of Clinical Neurophysiology (대한임상신경생리학회)
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Neuroprotective Effect of Rapamycin (Autophagy Enhancer) in Transgenic SOD1-G93A Mice of Amyotrophic Lateral Sclerosis

근위축성측삭경화증의 SOD1-G93A 유전자 이식 마우스 모델에서 라파마이신의 신경보호효과

  • Ahn, Suk-Won (Department of Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Jeon, Gye Sun (Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Park, Kwang-Yeol (Department of Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Hong, Yoon-Ho (Department of Neurology, Boramae Medical Center, Seoul National University College of Medicine) ;
  • Lee, Kwang-Woo (Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Sung, Jung-Joon (Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine)
  • 안석원 (중앙대학교 의과대학 중앙대학교병원 신경과학교실) ;
  • 전계선 (서울대학교 의과대학 서울대학교병원 신경과학교실) ;
  • 박광열 (중앙대학교 의과대학 중앙대학교병원 신경과학교실) ;
  • 홍윤호 (서울대학교 의과대학 보라매병원 신경과학교실) ;
  • 이광우 (서울대학교 의과대학 서울대학교병원 신경과학교실) ;
  • 성정준 (서울대학교 의과대학 서울대학교병원 신경과학교실)
  • Received : 2013.05.06
  • Accepted : 2013.07.01
  • Published : 2013.12.30
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Abstract

Background: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). Methods: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. Results: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. Conclusions: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.

Keywords

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