Can a coffee prevent Parkinson's disease?
Coffee
Coffee is one of the most-consumed beverage in the world. It is drunk alongside breakfast, at the end of the meal, during a break to increase attention or only to relax.
This beverage contains caffeine (a non selective antagonist of adenosine receptor) and the monoamine oxidase inhibitors β-carboline and harmane, which may contribute to its psychoactivity.
Some studies show that coffee has benefits on health, for example to reduce the risk of prostate cancer, Alzheimer's disease, dementia, heart disease, diabetes mellitus type 2, non-alcoholic fatty liver disease, cirrhosis, and gout.
Moreover seems that coffee can also prevents Parkinson's disease.
Parkinson's disease
Parkinson's disease is a neurodegenerative disorder caused by the death of dopaminergic neurons in the pars compacta of substantia nigra.
Pars compacta of substantia nigra is involved in two pathways of extrapyramidal sistem:
- Direct pathway
- Indirect pathway
The pathways have competing effects on movement : first pathway, stimulated, resulte in an activation of cerebral cortex while a stimulation of second pathway produce an inhibition.
Substantia nigra regulates this pathways with two dopamine receptors: D1 and D2.
Dopamine projections from the substantia nigra, pars compacta, to the striatum have complex, and ultimately opposing effects on activity in the direct and indirect pathways. For example, dopamine acts primarily through dopamine D1 receptors on the neurons that participate in the direct pathway, exciting these neurons. It acts on dopamine D2 receptors on the striatal neurons that are involved in the indirect pathway. The D2 receptors are inhibitory. Therefore, dopamine excites the direct pathway and inhibits the indirect pathway, with a net effect to increase facilitatory inputs to the motor regions. (The Basal Ganglia)
In hypokinesias – like parkinson’s disease - dopamine loss produces an overdone activation of indirect pathways producing in the patient typical symptoms of disorder (shaking, rigidity, slowness of movement and difficulty with walking and gait abnormaties).
(Parkinson's disease)
How coffee could prevent Parkinson's disease?
- first of all coffee contains caffeine (1,3,7-trimethylxanthine), a natural alkaloid that stimulates central nervous system and metabolism.
Whereas caffeine is both water-soluble and lipid-soluble, it readily crosses the blood–brain barrier that separates the bloodstream from the interior of the brain. Once in the brain, the principal mechanism of action is as a nonselective antagonist of adenosine receptors (in other words, an agent that reduces the effects of adenosine). The caffeine molecule is structurally similar to adenosine, and is capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive inhibitor.
Several classes of adenosine receptors have been described, with different anatomical distributions.A2A receptors are heavily concentrated in the basal ganglia, an area that plays a critical role in behavior control, but can be found in other parts of the brain as well, in lower densities. There is evidence that A 2A receptors interact with the dopamine system, which is involved in reward and arousal:
- Singh et al. have demonstrated that mice exposed to MPTP generate an alterate expression of A2a receptor if they are treated itraperitoneally daily with caffeine (20 mg/kg) for 8 weeks, followed by MPTP (20 kmg/kg) for 4 weeks or vice versa, along with respective controls.(Effect of caffeine on the expression of cytochrome P450 1A2, adenosine A2A receptor and dopamine transporter in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine treated mouse striatum,2009)
- Also Gòngora-Alfaro JL, studying with models of acute parkinsonism in rodents, have shown that caffeine reduces the loss of nigrostriatal dopaminergic neurons induced with the neurotoxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, effect that seems to be mediated through blockade of A(2A) adenosine receptors. Recently, it is illustrated that male rats treated with moderate doses of caffeine (5 mg/kg/day) during six months, followed by a withdrawal period of at least two weeks, developed a greater resistance to the catalepsy induced with the dopaminergic antagonist haloperidol, which was possibly mediated by an increase of dopaminergic transmission in the corpus striatum. (Caffeine as a preventive drug for Parkinson's disease: epidemiologic evidence and experimental support,2010)
- According to Popat RA et al. two ADORA2A (adenosine A2 receptor ) polymorphism (rs71651683 and rs5996696) were inversely associated with PD risk. (Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease,2011)
- Finally, Wills AM et al. have examined the possibility that adenosine A2A receptor antagonists - caffeine - reduce or prevent the development of dyskinesia in animal models of levodopa-induced dyskinesia. The results support the possibility that caffeine may reduce the likelihood of developing dyskinesia. (Caffeine consumption and risk of dyskinesia in CALM-PD,2013)
- Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system, in particular, by the CYP1A2 isozyme:
- Another study, followed by lee KW et al. proposed that another component of coffee - EHT (eicosanoyl-5-hydroxytryptamide) - could have a role in prevention of parkinson's disease. Mice fed a diet containing EHT for four weeks exhibited dose-dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed. Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment. The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT. (Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease,2013)
How coffee we can drink a day?
A cup of coffee contains 100 mg of caffeine. Different researches suggest that a moderate daily intake of 3-4 cup of coffee has convincing protective effects against development of Parkinson's disease. (Coffee can protect against disease,2012) (Caffeine and risk of Parkinson's disease in a large cohort of men and women,2012) (Coffee, caffeine-related genes, and Parkinson's disease: a case-control study,2008)
obviously,an excessive amounts of coffee can cause very unpleasant and even life-threatening adverse effects. Coffee's adverse effects are more common when taken in excess.
So, If we love coffee time, we can not fall out of the habit to consume our coffee cup.
