What are we learning about glutamate and Parkinson's disease?
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| There's good news |
For years we've been asking restaurants to omit the MSG because we get funky headaches later after eating foods containing this excitotoxin. We'v been reading food labels to avoid monosodium glutamate. We were already working on an article about glutamate and the role this protein building amino acid and neurotransmitter plays in Parkinson's disease. We learned a little about the good, the bad and the ugly in the process.
We know that glutamate is a rapid, excitatory transmitter and that it can be associated to a vulnerability to addiction, so perhaps you could call it the smoker's nemesis. We also know that glutamate receptors are necessary for proper central nervous system functioning, for important cognitive function including memory formation and learning.
This week everyone is talking about glutamate and GRIN2A because of the news from the World Parkinson's Congress currently being held in Glasgow, Scotland.
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| The coffee cups are waiting |
It has been learned that GRIN2A, is the "coffee" gene which when combined with caffeine intake appears not only to be neuroprotective for PD in a certain percentage of the population but may also affect PD clinical trial results when some study participants may have the altered GRIN2A gene. This in turn raises the question of whether it can also influence medications used to treat Parkinson's disease symptoms.
Those people protected by the caffeine gene are carriers of a specific variation of GRIN2A according to information discussed at the World Parkinson's Congress. At this time the focus is on a limited population.
We already know from the long Hawaii coffee study that people who had regular caffeine intake were (48%-84%) less likely to develop Parkinson's disease. It would be more than interesting to know how many members of this study also had the special GRIN2A gene version. But that was then and we didn't have the same technology or gene bank.
GRIN2A is a glutamate NMDA subunit receptor in a class of ionotropic glutamate gated ion channels, permeable to calcium. There has already been research about Bipolar disorder, ADHD and Huntington's disease as well as Parkinson's disease in connection to a hypoglutaminergic condition being involved in the pathogenesis. And certainly the negative role of glutamate in Parkinson's development is not unknown.
Researchers have been looking at the GRINB2 subunits for many years and their connection to PD in the forms of selective antagonists which can exacerbate levodopa-induced dyskinesia in animal models. In other animal studies it was discovered that loss of striatal dopamine led to an increased stimulation of NR2B aka GRIN2B which contains NMDA receptors.
Basically glutamate becomes a link in the nitric oxide chain. Under certain conditions glutamate can break through the outer cell membrane via the NMDA (n-methyl-d-asparatate) receptors located on the neurons. This creates a breach through which calcium can enter the cell. We already know that calcium is implicated in the death of dopamine neurons. If this chain can be interrupted...
To read more about the 2010 World Parkinson's Congress and to see folksy photos, check out Talk Parkinson's.
Additional reading:
Gene reference: GRIN2A
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