Penicillium

Ano et al. [ 43 54 ] identified oleamide and dehydroergosterol as two components of Camembert cheese that were responsible for suppressing microglial inflammation. Oleamide is an amide of oleic acid [ 55 56 ] ( Figure 1 ) that forms naturally in the body of animals and might be synthesized during the fermentation of dairy products byfungi [ 57 ]. Oleamide accumulates in the cerebrospinal fluid during sleep deprivation and induces sleep in animals; thus, it has potential applications in the treatment of mood and sleep disorders [ 58 59 ]. Oleamide not only suppresses the production of inflammatory cytokines and chemokines but also increases the microglial phagocytosis of Aβ. In addition, it induces the differentiation of microglia into the anti-inflammatory M2 type. A recent study using murine macrophages showed that oleamide suppressed the induction of iNOS and COX-2 by lipopolysaccharides (LPS) via preventing the nuclear translocation of NF-κβ by suppressing the phosphorylation of Iκβ-α [ 60 ]. Oleamide is also known as an endogenous substance that binds to cannabinoid receptor 2 (CB2), which is mainly expressed on the surface of immune cells (monocytes, macrophages, and B cells). CB2 is also expressed on microglia and contributes to the inhibition of microglia-mediated neurotoxicity by reducing the production of pro-inflammatory molecules [ 61 ]. In addition, CB2 activity facilitates the transformation of microglial cells from the M1 to M2 phenotype, which is suggested to favor phagocytosis and reparative mechanisms [ 62 ]. Several studies have proposed a direct role for CB2 in the modulation of Aβ peptide levels in the brain. Most of those studies have suggested that CB2 participates in Aβ clearance rather than in Aβ production and aggregation. In the case of amyloid precursor protein/presenilin 1 mice lacking CB2, the increased Aβ deposition observed may be related to a reduced phagocytotic activity of microglia in their brains [ 63 ], considering the role of CB2 activity in promoting microglial-induced Aβ phagocytosis [ 64 65 ]. These reports support the contention that oleamide, which is an agonist of CB2, suppresses the microglial inflammation and enhances the phagocytosis of Aβ, resulting in a preventive action against Alzheimer’s disease. CB2 has been receiving increasing attention as a therapeutic target for Alzheimer’s disease [ 66 68 ]. Ano et al. discovered that the concentration of oleamide in dairy products depends on the type of dairy product and the fermentation process used. Therefore, the dietary intake of oleamide can be increased via supplementation or the consumption of specific dairy products.