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Combined GSK-3 inhibitor and Nrf2 activator therapies may be an advantage, as additive protective effects against A toxicity are observed with Keap1 mutation and lithium treatment in the fly (Kerr et al., 2017) and DMF has recently been shown to prevent tau phosphorylation through inhibition of GSK-3 and neuronal damage by subsequent activation of Nrf2 through Keap1 dependent and independent mechanisms (Cuadrado et al., Neuro-Inflammation: TLR4/NFB and STAT3 as Anti-inflammatory Mediators of Lithium-Mediated Neuroprotection Alterations in microglia activation and inflammatory factors are an early feature in the brains of dementia patients, including AD and vascular dementia (Calsolaro and Edison, 2017) and viral infection (Hosseini et al., 2018) in mice, suggesting a causal link between inflammatory dysregulation and memory impairment

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Biochim Biophys Acta Mol Basis Dis 1822:690713