Table 6.
The proposed mechanism of the protective effect of metformin for SCI.
| References | Proposed mechanism | Effects |
|---|---|---|
| Wu et al. (2021) | Regulation of AMPK and mTOR signaling to enhance autophagy | Increased p-AMPK, ATG7, LC3-II and LAMP1, and decreased p-mTOR and p62 |
| Zhao et al. (2021) | Activation of TET2-FoxO3a axis | Increased TET2, enhanced interaction between TET2 and Foxo3a |
| Wang et al. (2020) | 1. Regulation of mitochondrial dysfunction and oxidative stress 2. stabilizing microtubule | 1. Increased p-AKT, Nrf2, HO-1, NQO1 and mitochondrial membrane potential, inhibited ROS 2. Increased Ace-tubulin and MAP2, and decreased Tyr-tubulin |
| Zhang et al. (2020) | Regulation of Wnt/β-catenin signaling | Increased β-catenin |
| Guo et al. (2019) | Alleviation of endoplasmic reticulum stress | Decreased GRP78, CHOP, caspase-12, and cleaved caspase-3 |
| Afshari et al. (2018) | Inhibition of neuroinflammation | Decreased TNF-α and IL-1β |
| Guo et al. (2018) | Inhibition of mTOR signaling to enhance autophagy | Decreased mTOR, p70S6K and p62, increased Beclin1, and LC3-II/ I ratio |
| Wang et al. (2018) | Regulation of AMPK and mTOR signaling | Increased p-AMPK, LC3-II/I ratio and Beclin 1, decreased p-mTOR, p-p70S6K, and p62 |
| Zhang et al. (2017a) | Regulation of AMPK and mTOR signaling to enhance autophagy | Increased p-AMPK, LC3-II and Beclin 1, decreased p-mTOR, p-p70S6K and p62 |
| Zhang et al. (2017b) | 1. Inhibiting neutrophil infiltration 2. Regulation of AMPK signaling | 1. Decreased ICAM-1 and MMP-9 2. Increased p-AMPK |
| Wang et al. (2016) | 1. Regulation of mTOR signaling to enhance autophagy 2. Suppressing neuroinflammation and apoptosis | 1. Decreased p-mTOR, p-p70S6K, increased LC3B-II and Beclin 1 2. Decreased NF-κB, cleaved caspase-3, increased Bcl-2 |
| Lin et al. (2015) | Regulation of AMPK signaling | Increased p-AMPK |
Ace-tubulin, acetylated tubulin; AKT, protein kinase B; ATG7, autophagy related protein 7; Bcl-2, B cell lymphoma-2; CHOP, CCAAT/enhancer-binding protein homologous protein; FoxO3a, forkhead box O3a; GRP78, glucose-regulated protein 78; HO-1, heme oxygenase-1; IL-1β, interleukin-1 beta; LC3-II, light chain 3-II; LAMP1, Lysosomal-associated membrane protein 1; MAP2, microtubule-associated protein-2; MMP-9, matrixmetalloproteinase-9; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-kappaB; NQO1, NAD(P)H: quinone oxidoreductase 1; Nrf2, nuclear factor (erythroid-derived 2)-like; ROS, reactive oxygen species; TET2, Ten-eleven translocation-2; TNF-α, tumor necrosis factor-α; Tyr-tubulin, tyrosinated tubulin; p-AMPK, phosphorylated adenosine monophosphate-activated protein kinase; p70S6K, p70 ribosomal protein S6 kinase.