杏吧原创

Combination therapy to protect against Parkinson鈥檚

Decaf coffee and nicotine-free tobacco aren鈥檛 just for the health-conscious. Giving them to flies with a form of Parkinson鈥檚 disease has revealed that although coffee and cigarettes protect the brain, caffeine and nicotine aren鈥檛 responsible for the benefit.

If the compounds that put up this brain defence can be identified, they may offer a preventive Parkinson鈥檚 treatment where none currently exists, says , a neuroscientist at the University of Washington in Seattle, whose team led the new study.

鈥淲e think that there鈥檚 something else in coffee and tobacco that鈥檚 really important,鈥� he says.

Bad for body, good for brain?

Evidence for the protective effect of coffee and tobacco comes mostly from epidemiological studies which suggest that coffee-drinkers and smokers are less likely to develop Parkinson鈥檚 than abstainers.

鈥淎 lot of the field has gravitated to the idea that it鈥檚 caffeine and nicotine [that protects their brains],鈥� says Pallanck. But because these drugs are harmful in large amounts, it would be tough to find a way of using them as therapies.

To see if ingredients other than caffeine and nicotine might be providing the benefit, Pallanck鈥檚 team turned to fruit flies with a condition similar to Parkinson鈥檚 disease.

Mutant flies

The flies have mutations that kill off dopamine-producing neurons, which causes them to develop movement and cognitive problems like those characteristic of Parkinson鈥檚 in people. The same mutations are linked to hereditary forms of Parkinson鈥檚 in humans.

Pallanck鈥檚 team prepared several fly foods spiced up with normal coffee, decaffeinated coffee, smokeless 鈥渄ipping鈥� tobacco designed to allow nicotine absorption via the mouth, or a commercial nicotine-free tobacco. Then the researchers raised groups of flies on the various diets.

Normally, dopamine-producing neurons in the mutant flies die off as they age. But a diet featuring coffee and tobacco kept the neurons alive in all the flies tested at 20 days old, whether or not their food contained caffeine or nicotine.

What鈥檚 more, when pure caffeine or nicotine were added to the meals of other groups of flies, their dopamine neurons died off 鈥� just like those of flies whose food had no additive at all. 鈥淲e didn鈥檛 see any protective effects at all of caffeine and nicotine,鈥� Pallanck says.

Protective pathways

His team went on to identify a compound found in both decaf and normal coffee called cafestol that seems partially responsible for its neuro-protective effects. Cafestol activates a protein produced by flies called Nrf2, and the team found that blocking Nrf2 diminished coffee鈥檚 protective effect on dopamine neurons.

Blocking Nrf2 in flies fed tobacco also reduced its protective effects. Pallanck鈥檚 team is now searching for tobacco ingredients that activate Nrf2 鈥� and other ones that do the same in coffee. These compounds might one day be given to people to protect against Parkinson鈥檚.

Alternatively, new drugs could mimic the protective neural processes triggered by coffee and cigarettes.

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