Table 1.
Drugs targeting downstream mediators of lithium-mediated neuroprotection.
| Class | Drugs | Neuroprotection in vitro and in animal models of neurodegeneration | Reference |
|---|---|---|---|
| GSK-3 inhibitors | ATP competitive: Indirubin Paullones Thiazoles Arylindolemaleimide (SB-216763 and SB-415286) | Neuroprotection, synaptic maintenance, improved cognitive function, reduced tau phosphorylation and, in some cases Aβ accumulation, in mouse models of AD and FTD. | Eldar-Finkelman and Martinez (2011) |
| Non-ATP competitive: Thiadiazolidindiones (TDZD-8, NP12/tideglusib) L803-mts | |||
| IMPA inhibitor | L-690,330 | Enhanced degradation of mutant α-synuclein and huntingtin in PC12 neuroblastoma cells. | Sarkar et al. (2005) |
| Nrf2 activators | Triterpenoids (CDDO-MA, CDDO-EA, CDDO-TFEA) | Reduced oxidative stress, improved cognition and motor function in mouse models of AD and ALS. | Dumont et al. (2009), Neymotin et al. (2011) |
| 22h | Protected mouse primary neurons from amyloid-induced toxicity. | Kerr et al. (2017) | |
| Dimethyl fumarate (DMF) | Preserved viability against Aβ-induced toxicity in SHSY-5Y cell and mouse hippocampal slice cultures, and was neuro-protective in mouse models of PD and FTD. | Lastres-Becker et al. (2016), Campolo et al. (2018), Cuadrado et al. (2018) | |
| BDNF/TrkB activator | dihydroxyflavone (7,8-DHF) | Protected primary neurons from Aβ-induced toxicity, and promoted synaptogenesis. | Zhang et al. (2014) |
| mGluR inhibitors | MPEP (2-Methyl-6-(phenylethynyl)pyridine), and MTEP(2-Methyl-4-thiazolyl)ethynyl)pyridine | Prevented toxicity in neuronal cultures and AD and DLB mouse models. | Um et al. (2013), Overk et al. (2014) |
| BMS-94923 | Prevented Aβ-induced inhibition of synaptic plasticity, and rescued memory deficits in an AD mouse model. | Haas et al. (2017) | |
| TLR4 inhibitors | IAXO102 and FP7 | Protected toxicity in primary neurons from the SOD1G93A mice model of ALS. | De Paola et al. (2016) |
| Gx-50 | Prevented Aβ-induced microglial activation and neuro-inflammation in rat microglia and APPswe, PSEN1dE9 mice. | Shi et al. (2016) |