Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule
Joint Authors
Xiao, Jian
Xu, Ke
Li, Yao
Han, Wen
Wang, Haoli
Zheng, Zhilong
Yuan, Yuan
Zhou, Kailiang
Wang, Qingqing
Xie, Ling
Zhang, Hongyu
Xu, Huazi
Wu, Yanqing
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-07
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability.
Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention.
Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders.
However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear.
In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway.
Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo.
Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE).
Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect.
We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro.
Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction.
Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.
American Psychological Association (APA)
Wang, Haoli& Zheng, Zhilong& Han, Wen& Yuan, Yuan& Li, Yao& Zhou, Kailiang…[et al.]. 2020. Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-20.
https://search.emarefa.net/detail/BIM-1206128
Modern Language Association (MLA)
Wang, Haoli…[et al.]. Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-20.
https://search.emarefa.net/detail/BIM-1206128
American Medical Association (AMA)
Wang, Haoli& Zheng, Zhilong& Han, Wen& Yuan, Yuan& Li, Yao& Zhou, Kailiang…[et al.]. Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-20.
https://search.emarefa.net/detail/BIM-1206128
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1206128