... Moreover, both animal (Rahvar, Owji, & Mashayekhi, 2018) and human studies (Neshatdoust et al., 2016) showed that quercetin may affect BDNF levels through regulation of gene expression (Rahvar et al., 2018) and improve synthesis of nerve growth factor (NGF) and neurite outgrowth via an increase in intracellular Cl(−) by activating the Na(+)/ K(+)/2Cl(−) cotransporter isoform 1 (NKCC1) without any increase in the expression level of NKCC1 protein (Nakajima, Niisato, & Marunaka, 2011). Additional mechanism for the neuroprotective activity of quercetin and its cognitive-enhancing effect (Sriraksa et al., 2012) relates to the modulation of autophagy (Qu, Liang, Gu, & Liu, 2014;Regitz, Dußling, & Wenzel, 2014), the inhibition of Aβ aggregation (Sato et al., 2013) and prevention of Tau phosphorylation (Sabogal-Guáqueta et al., 2015), the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (Abdalla et al., 2014), G. Caruso, S.A. Torrisi, M.P. Mogavero et al. Pharmacology & Therapeutics xxx (xxxx) xxx the reduction of neuroinflammatory phenomena through the downregulation of iNOS, COX-2, TNF-α, IL-6, IL-1β, and interferon-γ (IFNγ) in microglia and macrophages Qureshi et al., 2011;Testa et al., 2014), and the activation of sirtuin 1 (SIRT1), which in turn would lead to the suppression of B-cell lymphoma 2 (BCL2)-associated X protein (Bax)-dependent apoptosis as well as the inhibition of several additional pro-apoptotic transcription factors (Leyton et al., 2015). ...