The Neuroprotective Effects of Eicosanoyl-5-hydroxytryptamide in an in vitro Model for Parkinson’s Disease

Abstract

Parkinson’s Disease (PD) is a neurodegenerative disorder that causes serious motor symptoms and impairs quality of life. Furthermore, coffee drinking is associated with a decreased risk of PD. This has guided research towards compounds in coffee that could serve as potential therapeutics for PD. A previously identified compound in coffee, eicosanoyl-5-hydroxytryptamide (EHT), has been shown to decrease aggregation and phosphorylation of disease-specific proteins in an α-synuclein transgenic mouse model. Also, EHT has also been shown to exhibit anti-inflammatory and anti-oxidant neuroprotective properties in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- treatment mouse model. Here, we study the cytoprotective effects of EHT in SH-SY5Y human neuroblastoma cells treated with 1-methyl-4-phenylpyridinium (MPP+) as an in vitro model for PD. EHT administration to SH-SY5Y cells demonstrated nanomolar efficacy in reducing MPP+-induced cellular cytotoxicity. This cytoprotective property was highly dependent upon EHT’s specific chemical structure, as demonstrated by studies on various EHT analogs. Moreover, our results suggested that the cytoprotective effect was likely due to EHT directly protecting against the adverse effects of MPP+, rather than blocking MPP+’s inhibition of mitochondrial complex I. Lastly, EHT’s mechanism of protection may involve more than simply the inhibition of demethylation of phosphoprotein phosphatase 2A (PP2A), a major serine/threonine phosphatase that has been implicated in PD disease progression. Altogether, our findings raise the possibility of EHT becoming a viable neuroprotective therapeutic for PD.