N-eicosanoyl serotonin is a natural product found in coffee which synergizes with caffeine in protecting the brain in models of α-synucleinopathy1. It inhibits the PP2A methylesterase maintaining PP2A in a highly active state leading to hypophosphorylated α-synuclein. In mouse models it preserved neuronal integrity and function, diminished neuroinflammation and improved behavioral performance. It prevents Aβ-induced impairments in mouse models of Alzheimer’s disease2,3.
1) Yan et al. (2018), Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson’s disease and DLB; Proc. Natl. Acad. Sci. USA, 115 E12053
2) Asam et al. (2017), Eicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid; PLoS One, 12 e0189413
3) Basurto-Islas et al. (2014), Therapeutic benefits of a component of coffee in a rat model of Alzheimer’s disease; Neurobiol. Aging, 35 2701