M. Maral Mouradian, M.D.
William Dow Lovett Professor of Neurology
Vice Chancellor for Faculty Development, Rutgers Biomedical and Health Sciences
Director, RWJMS Institute for Neurological Therapeutics
Rutgers -Robert Wood Johnson Medical School
Piscataway, NJ 08854
MedicalResearch.com: What is the background for this study?
Response: Drinking coffee has been known from epidemiological studies to be linked with reduced risk of developing Parkinson’s disease (PD).This protective effect has been traditionally attributed to caffeine, the best known compound present in coffee.
But coffee has more than a thousand different compounds. And among people with early PD, the amount of caffeine consumption does not impact how fast the disease progresses, raising some question about the protective effect of just caffeine in coffee. We previously found another compound in coffee, Eicosanoyl-5-hydroxytryptamide (EHT), which protects the brain in laboratory mice against a protein called alpha-synuclein that accumulates in abnormal forms in Parkinson’s disease and in Dementia with Lewy Bodies (DLB).
EHT is a fatty acid derivative of the neurotransmitter serotonin and is a principal constituent of coffee wax that coats the coffee bean. We had purified EHT from coffee in search for compounds that boost the activity of a catalyst enzyme called PP2A (B55alpha) that helps reduce the aggregation of alpha-synuclein. Our investigations had also shown that PP2A is less active in brains affected with PD and DLB than in normal age-matched controls. So, we hypothesized that enhancing PP2A activity may mitigate alpha-synuclein related pathology. In the present study, we wanted to find out if these two components of coffee, caffeine and EHT, can work together or cooperatively to protect the brain against the negative effects of abnormal alpha-synuclein.
MedicalResearch.com: What are the main findings?
Response: We tested this
idea in two models of alpha-synuclein related pathology in laboratory mice. One
model has excess of this protein throughout the brain (transgenic), and the
other model is generated by injecting the abnormal fibrillar form of
alpha-synuclein in a brain region connected with dopamine producing neurons
that degenerate in PD. In the latter model, abnormal alpha-synuclein aggregates
have been shown to propagate to other brain regions including dopamine neurons.
We found that small doses of either EHT or caffeine given alone were ineffective in preventing alpha-synuclein aggregation or propagation, and could not protect the brain against the toxicity of alpha-synuclein. On the other hand, the combination of the two compounds could. This was accompanied with preserved neuronal integrity and function, diminished neuroinflammation, and improved behavioral performance on motor and memory tasks. We also found that this synergistic beneficial action between EHT and caffeine is through boosting the activity of PP2A.
MedicalResearch.com: What should readers take away from your report?
Response: Our findings suggest a potential therapeutic option to slow down or stop the progression of Parkinson’s disease and Dementia with Lewy Bodies. This is in contrast to the currently available treatments for PD that only help some of the motor symptoms but do not impact the brain degeneration.
The treatment approach we tested in this study uses two natural products that people normally ingest. But it will be important for us to find the proper amount that could be protective for the brain in people. Our findings from the combination of the two compounds also mean that caffeine does not need to be consumed in large amounts for it to protect the brain in Parkinson’s disease and DLB so long as it is taken in combination with EHT. This can minimize the negative health consequences of consuming too much caffeine.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: As in any research and development effort in the discovery of new treatments for diseases, the next necessary step is to test this combination treatment in people with Parkinson’s disease and DLB in properly designed clinical trials. Importantly, the amounts of EHT and caffeine in combination needed for the protective effect in people with these diseases have to be determined.
MedicalResearch.com: Is there anything else you would like to add?
Response: This study was carried out in collaboration with Princeton University and funded by a research grant from the National Institutes of Health. The senior scientists are inventors of a patent application relevant to this work.
The original publication is freely available at: https://www.pnas.org/content/early/2018/11/26/1813365115.long
Run Yan, Jie Zhang, Hye-Jin Park, Eun S. Park, Stephanie Oh,Haiyan Zheng, Eunsung Junn, Michael Voronkov, Jeffry B. Stock, M. Maral Mouradian. Synergistic neuroprotection by coffee componentseicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson’s diseaseand DLB. Proceedings of the National Academy of Sciences,2018; 201813365 DOI: 10.1073/pnas.1813365115
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