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.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAT1-SM (25))
Program Officer
Hopp, Craig
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Medicine & Dentistry of NJ
Schools of Medicine
United States
Zip Code
Lee, Kang-Woo; Woo, Jong-Min; Im, Joo-Young et al. (2015) Apoptosis signal-regulating kinase 1 modulates the phenotype of ?-synuclein transgenic mice. Neurobiol Aging 36:519-26
Potts, Lisa F; Uthayathas, Subramaniam; Greven, Alexander C M et al. (2015) A new quantitative rating scale for dyskinesia in nonhuman primates. Behav Pharmacol 26:109-16
Choi, Doo Chul; Chae, Yoon-Jee; Kabaria, Savan et al. (2014) MicroRNA-7 protects against 1-methyl-4-phenylpyridinium-induced cell death by targeting RelA. J Neurosci 34:12725-37
Grosso, Hilary; Woo, Jong-Min; Lee, Kang-Woo et al. (2014) Transglutaminase 2 exacerbates ?-synuclein toxicity in mice and yeast. FASEB J 28:4280-91
Lee, Kang-Woo; Im, Joo-Young; Woo, Jong-Min et al. (2013) Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease. Neurotherapeutics 10:143-53