TABLE 2.
Summary of literature evidence for prioritized drugs obtained from Gene2Drug analysis.
| Drugs | Gene list | Summary of evidence (drug targets) | Toxicity |
|---|---|---|---|
| Ellipticine | Excitatory neuron | • Inhibition of proinflammatory cytokines (TNF-α, IL-6), oxidative stress, Aβ production, early apoptosis signal by direct suppression of JNK-AP-1 pathway Krilleke et al. (2003); Tian et al. (2019) | Mild side effects such as nausea, vomiting, hypertension, muscular cramp. O'sullivan et al. (2013) |
| Oligodendrocyte | |||
| Alsterpaullone | Excitatory neuron | • Reduction of cytoskeletal abnormalities, neuronal death, tau hyperphosphorylation, Aβ formation by inhibiting GSK-3β and CDK5. Leost et al. (2000); Phiel et al. (2003); Shrestha et al. (2013); Maqbool et al. (2016) | May have mild side effects such as diarrhea, nausea, vomiting. Senderowicz (2000) |
| Astrocyte | • May promote hippocampal neurogenesis, proliferation and differentiation Maqbool et al. (2016) | ||
| • To a lesser extent: Additional effects on limiting early toxic protein deposition and glial cell-mediated neuroinflammation regulated by ERK1/2. Inoue et al. (2012); Sun and Nan (2017) | |||
| Tomelukast | Excitatory neuron | • Inhibition of CysLT1 involved in neuroinflammation, cell apoptosis, disrupted BBB and vasculature, disrupted learning and memory Hoover (1990); Michael et al. (2019) | Damage to liver; gastrointestinal: Hypermotility, diarrhea Hoover (1990) Hagopian (1988) |
| Oligodendrocyte | • Increasing anti-inflammatory cytokines and neuroprotective molecules (HSP70, IkBα, and IkBβ) by activating PPAR-γ Feinstein (2004) | ||
| Ginkgolide A | Astrocyte | • Modulating post-translational modifications of α-tubulin to preserve microtubule dynamics. Zhang et al. (2015); Kawamura et al. (2016) | Mild side effects such as headache, nausea, vomiting, allergic skin reactions. Gornik and Creager (2013) |
| • Inhibitor of NMDA receptor involved in impaired neurotransmission and cognitive decline Kuo et al. (2018) | |||
| • Reduction of phosphorylated tau proteins by activating PI3K-Akt pathway to phosphorylate GSK3β at ser9. Dudek et al. (1997); Chen et al. (2012) | |||
| Chrysin | Oligodendrocyte | • Reduction of neurotrophic factors (NO, TNF-α) by downregulating NF-kB p65 and C/EBPs Gresa-Arribas et al. (2010) | Chrysin has been shown to induce toxicity in trout liver cells Siddiqui et al. (2018) |
| • Improvement of memory function in the hippocampus caused by Aβ deposition Vedagiri and Thangarajan (2016) | |||
| • Upregulation of antioxidative and cytoprotective genes (HO-1, CAT and SOD) by activating Nrf2 under oxidative stress Angelopoulou et al. (2020) | |||
| • Promotion of cell survival and inhibition of mitochondrial dysfunction and autophagy dysregulation through activation of MEF2D Angelopoulou et al. (2020) | |||
| Ouabain | GWAS | • Reduction of pro-inflammatory cytokines by inhibiting Na+/K+ - ATPase involved in upregulating NF-kB and NLRP3. de Lores Arnaiz and Ordieres (2014) | Mild side effects: Nausea, vomiting, pulse irregularities |
| • Enhancement of TFEB in which to increase APP and tau degradation. Xiao et al. (2015) | |||
| Sulindac sulfide | Excitatory neuron | • May slow neuronal aging, memory deficits and prevent early accumulation of Aβ oligomers induced by COX. Lee et al. (2008); Woodling et al. (2016) | Gastrointestinal effect including ulceration, bleeding and perforation Park (1982) |
| • Preferential inhibition of γ42-secretase to decrease Aβ42 aggregation Takahashi et al. (2003) | |||
| • Reduction of proinflammatory cytokines and APP aggregation by augmenting PPAR-γ Khan et al. (2019) | |||
| Lorglumide | Oligodendrocyte | • Reduction of dopamine neurotransmission by regulating CCKA receptor. Gonzalez-Puga et al. (2005); Ballaz, 2017) | Mild side effects Makovec et al. (1987) |