PT  - JOURNAL ARTICLE
AU  - Huber, Kristen
AU  - Voronkov, Michael
AU  - Fernandez, Jose
AU  - Rouzard, Karl
AU  - Iishi, Akira
AU  - Perez, Eduardo
AU  - Stock, Maxwell
AU  - Stock, Jeff
TI  - EHT™ coffee extract: A neuroprotective agent and modulator of PP2A methylation with anti-inflammatory and antioxidant properties (S16.006)
DP  - 2015 Apr 06
TA  - Neurology
PG  - S16.006
VI  - 84
IP  - 14 Supplement
4099  - http://n.neurology.org/content/84/14_Supplement/S16.006.short
4100  - http://n.neurology.org/content/84/14_Supplement/S16.006.full
SO  - Neurology2015 Apr 06; 84
AB  - OBJECTIVE: A reduced risk of neurodegeneration has been highlighted in epidemiological studies simply by consuming coffee. However the mechanism by which this occurs remains unknown. Thus, we sought to elucidate a specific component in coffee, which could be a modulator of PP2A phosphatase activity and provide neuroprotective properties. BACKGROUND: Protein Phosphatase 2A (PP2A), the major serine/threonine phosphatase in the brain, has been implicated in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease due to its reduced activity and methylation of its carboxy-terminal. The discovery of novel modulators of PP2A phosphatase activity from natural sources might provide a beneficial outcome in CNS therapeutics. Epidemiological studies about dementia suggested that daily coffee consumption provided a decreased risk of dementia/AD by about 65[percnt]. Interestingly, this protection seems to be specific to coffee and does not extend other caffeinated beverages. DESIGN/METHODS: Activity of the PP2A methylation system was monitored via tritium labeling of the carboxy-terminus using 3H-SAM. To study neuroprotection, SH-SY5Y neuroblastoma cells challenged with neurotoxin MPTP, in the presence or absence of EHT, were analyzed for LDH release. A pro-oxidative NADPH/ADP/FE3+-microsomal assay system was used to study the antioxidant properties while anti-inflammatory properties were studied via pro-inflammatory cytokine inhibition in a TPA-induced cell-based assay. RESULTS: In this study, a component in coffee called eicosanoyl-5-hydoxytryptamide, or EHT, has been identified to prevent demethylation of PP2A in vitro with an IC50 of 5μM. Furthermore, EHT protected SH-SY5Y cells from MPTP induced toxicity and also exhibits antioxidant and anti-inflammatory properties comparative to Vitamin E and clobetasol respectively. CONCLUSIONS: EHT has been shown to work through several mechanisms including having anti-inflammatory and antioxidant activities as well as its ability to modulate the activity of PP2A. These findings indicate that EHT is one of the components responsible for the neuroprotective properties of coffee.Disclosure: Dr. Huber has received personal compensation for activities with Signum Biosciences as an employee. Dr. Voronkov has received personal compensation for activities with Signum Biosciences as an employee. Dr. Fernandez has received personal compensation for activities with Signum Biosciences, Inc. as an employee. Dr. Rouzard has received personal compensation for activities with Signum Biosciences, Inc. Dr. Iishi has received personal compensation for activities with Signum Biosciences, Inc.. as an employee. Dr. Perez has received personal compensation for activities with Signum Biosciences, Inc. Dr. Stock has received personal compensation for activities with Signum Biosciences as an employee. Dr. Strock has received personal compensation for activities with Signum Biosciences as a scientific advisory board participant.Tuesday, April 21 2015, 3:15 pm-5:00 pm