TNF and major depressive disorder: Nattokinase has been demonstrated to improve the Aβ-induced cognitive impairment, as well as anxiety-, depression-like behavior in mouse models of AD, possibly via the downregulation of the pro-inflammatory cytokines IL-6 and TNF-α, as well as the upregulation BDNF and the anti-inflammatory cytokine Il-10 [123].These findings suggest that these agents might hold a promising therapeutic potential in MBI and especially the domains of affective dysregulation and apathy in AD, mainly through their effects on the HPA axis regulation and neuroinflammatory responses.