Coffee is by far the most widely and highly consumed herbal extract. Numerous epidemiological studies indicate that coffee consumption affords reduced risk of Parkinson's disease (PD). This association has been attributed to caffeine, but coffee is much more than just caffeine and the finding that caffeine may be neuroprotective in no way obviates the possibility that other components in coffee may play a synergistic role with caffeine. We have recently isolated a lipid-like component of coffee, EHT, and found it to have a protective effect in mouse models of PD. Biochemical and neuropathological analyses demonstrate that dietary supplementation with EHT leads to decreased ?-synuclein phosphorylation and aggregation, a robust anti-inflammatory effect, and protection against oxidative stress. Studies indicate that the actions of caffeine stem from its antagonism of adenosine A2A receptor signaling, but downstream neuroprotective mechanisms remain to be established. The proposed research will elucidate the molecular mechanisms of neuroprotection mediated by caffeine and EHT as well as their synergy through in vitro biochemical analyses, cell based molecular experiments and in vivo studies in mouse models of PD. The ultimate goal of this work is to develop a dietary supplement(s) or medical food that would slow the progression or prevent the development of neurodegenerative disorders such as PD.

Public Health Relevance

Coffee, which by far is the most widely and highly consumed herbal extract worldwide, has been linked to reduced risk of developing Parkinson's disease. While this effect has been attributed largely to caffeine, coffee has many more components than just caffeine. This project focuses on understanding the mechanisms by which certain coffee constituents protect brain cells. The ultimate goal of this work is to develop a dietary supplement(s) that would slow the progression or prevent the development of neurodegenerative disorders including Parkinson's disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT006868-04
Application #
8734228
Study Section
Special Emphasis Panel (ZAT1)
Program Officer
Hopp, Craig
Project Start
2012-09-30
Project End
2017-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Rbhs-Robert Wood Johnson Medical School
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Oh, Stephanie E; Park, Hye-Jin; He, Liqiang et al. (2018) The Parkinson's disease gene product DJ-1 modulates miR-221 to promote neuronal survival against oxidative stress. Redox Biol 19:62-73
Oh, Stephanie E; Mouradian, M Maral (2018) Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transduction. Redox Biol 14:211-217
Park, Hye-Jin; Lee, Kang-Woo; Oh, Stephanie et al. (2018) Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease. J Neuropathol Exp Neurol 77:139-148
Yan, Run; Zhang, Jie; Park, Hye-Jin 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 U S A 115:E12053-E12062
Oh, Stephanie E; Mouradian, M Maral (2017) Regulation of Signal Transduction by DJ-1. Adv Exp Med Biol 1037:97-131
Asam, Kesava; Staniszewski, Agnieszka; Zhang, Hong 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
Phukan, Geetika; Shin, Tae Hwan; Shim, Jeom Soon et al. (2016) Silica-coated magnetic nanoparticles impair proteasome activity and increase the formation of cytoplasmic inclusion bodies in vitro. Sci Rep 6:29095
Park, Hye-Jin; Lee, Kang-Woo; Park, Eun S et al. (2016) Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies. Ann Clin Transl Neurol 3:769-780
Chaudhuri, Amrita Datta; Kabaria, Savan; Choi, Doo Chul et al. (2015) MicroRNA-7 Promotes Glycolysis to Protect against 1-Methyl-4-phenylpyridinium-induced Cell Death. J Biol Chem 290:12425-34
Aung, Latt Latt; Mouradian, M Maral; Dhib-Jalbut, Suhayl et al. (2015) MMP-9 expression is increased in B lymphocytes during multiple sclerosis exacerbation and is regulated by microRNA-320a. J Neuroimmunol 278:185-9

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