Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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The Effect of Exercise Training on Aβ-42, BDNF, GLUT-1 and HSP-70 Proteins in a NSE/ APPsw-transgenic Model for Alzheimer's Disease.

지구성 운동이 NSE/APPsw 알츠하이머 질환 생쥐의 인지능력, Aβ-42, BDNF, GLUT-1과 HSP-70 단백질 발현에 미치는 영향

  • Eum, Hyun-Sub (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kang, Eun-Bum (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Lim, Yea-Hyun (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Lee, Jong-Rok (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Cho, In-Ho (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kim, Young-Soo (Korea Institute of Sport Science) ;
  • Chae, Kab-Ryoung (Division of Laboratory Animal Resources, and National Institute of Toxicological Research, Korea FDA) ;
  • Hwang, Dae-Yean (College of National Resources & Life Science, Pusan National University) ;
  • Kwak, Yi-Sub (Department of Physical Education, Dong-Eui University) ;
  • Oh, Yoo-Sung (Department of Physical Education, Seoul City University) ;
  • Cho, Joon-Yong (Exercise Biochemistry Laboratory, Korea National Sport University)
  • 엄현섭 (한국체육대학교 체육과학관 운동생화학실) ;
  • 강은범 (한국체육대학교 체육과학관 운동생화학실) ;
  • 임예현 (한국체육대학교 체육과학관 운동생화학실) ;
  • 이종록 (한국체육대학교 체육과학관 운동생화학실) ;
  • 조인호 (한국체육대학교 체육과학관 운동생화학실) ;
  • 김영수 (체육과학연구원) ;
  • 채갑룡 (식약청 독성연구소 실험동물자원실) ;
  • 황대연 (부산대학교 생명응용과학부) ;
  • 곽이섭 (동의대학교 체육학과) ;
  • 오유성 (서울시립대학교 생활체육학과) ;
  • 조준용 (한국체육대학교 체육과학관 운동생화학실)
  • Published : 2008.06.30
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Abstract

Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

알츠하이머 질환은 신경퇴행성질환으로 노령인구에서 뿐만 아니라 $30{\sim}60$세 사이에서도 상염색체성우성형으로 발생하여 사회문제로 대두되고 있으며 발병기전도 명확하게 규명되지 않은 상태이다. 따라서 이 연구에서는 hAPP695sw 돌연변이를 neuron-specific enolase (NSE) 유전자의 프로모터 조절 하에 연결시킨 융합 유전자(pNSE/APP695sw fusion gene)를 과 발현시킨 알츠하이머 질환 모델생쥐를 대상으로 16주간 지구성 운동에 따른 알츠하이머 질환 모델생쥐의 인지능력의 변화와 주병변인 $A{\beta}-42$ 단백질과 함께 GLUT-1, BDNF, HSP-70 단백질의 발현량을 분석하였다. 그 결과 지구성 운동은 APPsw 알츠하이머 질환 모델생쥐의 인지능력을 개선시키는데 긍정적인 영향을 미친 것으로 나타났으며 이러한 인지능력의 개선은 알츠하이머 질환의 주 병변인 뇌의 $A{\beta}-42$ 감소뿐만 아니라 BDNF, GLUT-1과 HSP-70 단백질의 발현 증가와 관련이 있음을 확인하였다. 따라서 지구성 운동은 약물 처치 이외에 알츠하이머 질환을 예방하거나 지연시킬 수 있는 전략적인 방법으로 활용할 수 있음을 알 수 있다.

Keywords

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