SOME PEOPLE鈥檚 brain cells may become damaged because their bodies are relatively poor at removing particular toxins, according to a team of British neuroscientists. If the researchers are correct, then our understanding of incurable conditions such as Parkinson鈥檚 and motor neurone disease could be radically altered.
The team has found certain enzymes that behave abnormally in people with Parkinson鈥檚, motor neurone disease and Alzheimer鈥檚 鈥� conditions in which nerve cells degenerate progressively. Because these enzymes break down compounds that are foreign to the body, and because some of the compounds are known to be toxic to the brain, it is possible that such people are unusually vulnerable to brain damage by slow, chronic poisoning, says the team.
Adrian Williams, Glyn Steventon, Rosemary Waring and their colleagues at the University of Birmingham reported their latest results at a meeting in London to mark the 21st birthday of the Parkinson鈥檚 Disease Society. Some of their data will also be published this month in Neurology.
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If the early research can be taken further, the scientists believe its implications could be far-reaching. 鈥業t could be that whatever happens in the brain 鈥� however interesting it is 鈥� is not the real problem,鈥� says Williams. Instead, the body鈥檚 defence mechanisms against toxins may need much more study, to determine whether they are genetically controlled, for example.
Several teams have already linked aluminium in the diet with the development of Alzheimer鈥檚 disease. But no one has looked thoroughly at the way the body defends itself against the toxins in our ordinary foods 鈥� such as sulphur compounds in vegetables.
One important implication of the studies is that some of the abnormal enzymes might be useful as 鈥榤arkers鈥� to identify people with early stages of the diseases, or people at risk of developing them. This would eventually raise the question of whether to screen people and advise those found to be vulnerable to avoid certain substances in food.
Williams and his colleagues have already identified an enzyme, monoamine oxidase type B (MAO-B), that is abnormal in people with Parkinson鈥檚 and which they say could be a marker for people at risk of developing the disease (The Lancet, vol 335, p 180).
The team measured the enzyme鈥檚 activity in blood samples from 40 patients with early, untreated Parkinson鈥檚, and compared these with samples from healthy controls. MAO-B was much less active in the Parkinson鈥檚 samples than in the controls.
女生小视频s already have evidence that a drug called selegiline can slow the progression of Parkinson鈥檚 (New 女生小视频, Science, 17 March). 鈥業f you can pick up the disease up to 30 years beforehand, you might be able to slow or even prevent it with this drug,鈥� says Williams.
MAO-B helps to break down certain neurotransmitters, or chemical messengers, in the brain. One such neurotransmitter is dopamine. People with Parkinson鈥檚 have too little dopamine because the cells that produce it are degenerating. Selegiline inhibits the action of MAO-B, and so conserves the limited supply of dopamine.
Another function of MAO-B is to break down a compound known as MPTP. This compound is a black-market drug and produces acute symptoms that resemble Parkinson鈥檚 in people who inject it into their veins (see 鈥楾he intricate wiring that lets us move鈥�, New 女生小视频, 10 March).
In the liver, MAO-B turns MPTP into another compound, MPP+. This cannot cross the blood-brain barrier and is normally excreted. But if someone injects MPTP, it bypasses the liver and enters the brain, where it is converted to MPP+. MPP+ is highly toxic in the brain, because it destroys the cells that produce dopamine.
The researchers speculate that in people with Parkinson鈥檚, MAO-B may be less effective than normal in breaking up MPTP in the liver, so that the excess compound can reach the brain via the blood. 鈥業t remains a possibility that there is an MPTP-like substance lurking somewhere in our diet,鈥� says Williams.
The team has also found that people with early symptoms of Parkinson鈥檚, Alzheimer鈥檚 or motor neurone disease all fail to break down certain sulphur compounds as effectively as healthy controls (Neuroscience Letters, vol 110, p 216). Sulphur is present in some vegetables, and hydrogen sulphide, a known toxin, is made in the gut by bacteria acting on certain foods. The researchers now know that thiolmethyltransferase, an enzyme that breaks down some sulphur compounds, is abnormal in these people.
It is far too soon to conclude that the diseases are caused by a combination of genetic vulnerability and environmental exposure, say the researchers, but the evidence is tantalising.
