Characterizing the Synthesis and Degradation of N-acylserotonins in Murine Tissues

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common neurodegenerative diseases, both of which involve symptomatic hyperphosphorylated neuronal proteins. It is thought that AD and PD might be treated by activating PP2A, the major phosphatase in the brain. Previous studies have linked eicosanoyl-5-hydroxytryptamide (EHT) with activation of PP2A and attenuation of symptoms in numerous in vitro and in vivo models of AD and PD. Existing work has focused on isolating and characterizing the enzyme responsible for its synthesis in mammals. Here, we confirmed via mass spectrometry that murine intestinal extracts synthesize EHT enzymatically. We also began efforts to purify the extract, with a nearly tenfold increase in specific activity over previous extracts. Additionally, this thesis initiated the search for an enzyme responsible for degrading EHT. As of this writing, no hydrolysis has been observed in various preparations of murine tissues.