Neuroprotective Effect of Rapamycin (Autophagy Enhancer) in Transgenic SOD1-G93A Mice of Amyotrophic Lateral Sclerosis |
Suk-Won Ahn1, Gye Sun Jeon2, Kwang-Yeol Park1, Yoon-Ho Hong3, Kwang-Woo Lee2, and Jung-Joon Sung2 |
1Department of Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul 2Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 3Department of Neurology, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea |
Corresponding Author:
Jung-Joon Sung ,Tel: +82-2-2072-2820, Fax: +82-2-3672-7553, Email: jjsaint@snu.ac.kr |
Received May 6, 2013 Accepted July 1, 2013 |
Copyright © 2013 The Korean Society of Clinical Neurophysiology |
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium,
provided the original work is properly cited. |
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. |
Key words:
Autophagy, Rapamycin, Amyotrophic lateral sclerosis, ALS |
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