A study carried out by Catalan researchers shows that oxidative stress and damage to certain macromolecules are involved in the progression of Huntington’s Disease (HD), which is characterised by psychiatric and cognitive disturbance, involuntary movements (chorea) and dementia.
The research was carried out using human brain samples obtained post mortem from people affected by HD, which were compared with samples from control patients (C) who had died from unrelated illnesses or other causes. The two cerebral areas most affected by this illness – the striate cortex and cortex – were studied.
The samples, which were provided by the tissue bank at the University of Barcelona’s Institute of Neuropathology, were divided into HD-C group pairs based on gender, age, and the length of time after death before the tissue had been removed.
“Bidimensional electrophoresis techniques were used to compare the differences between the proteins present in the brains of the sick people and those of the controls,” said Elisa Cabiscol, professor of biochemistry at the University of Lleida, and one of the report’s authors. “The results showed that more than half of these were enzymes related to antioxidant defence systems.”
This study, which used human samples for the first time and was funded by Spain’s Consolider-Ingenio 2010 Programme, found that the brain tissue from people suffering from HD had elevated levels of proteins that eliminate reactive oxygen species (ROS), or free radicals, as they are more commonly known.
“There is a situation we call oxidative stress in the brains of these patients, and as a result the neurones (and other cells in the brain, such as the glia cells) attempt to defend themselves by increasing their antioxidant defences,” said Cabiscol.
In normal conditions, the balance between ROS generation and antioxidant systems allows cells to function correctly. However, in a situation of oxidative stress, ROS generation exceeds the cells’ defence capacity, causing changes in the cells that ultimately cause them to die.
“Our proteomic study has made clear how important a role oxidative stress plays in this illness, calling for the use of therapeutic strategies that boost antioxidant defences or prevent the formation of ROS, on order to try to halt or slow down the progression of this devastating disease,” added the researcher.
HD is caused by degeneration of cells in the brain, the neurones, as a result of genetic changes. The symptoms of this disease that runs in families first become apparent in middle age, and it progresses over 15 to 20 years before leading to an inevitable death. Both the speed at which the disease progresses and the age of onset varies from one person to another.
Mutation on the /htt/ gene generates an abnormal protein (huntingtin), which has a ‘polyglutamine tail’. These polyglutamines eventually cause the protein to form aggregates. “What we still don’t understand is the function of this protein, and how the presence of these aggregates causes the neurones in certain areas of the brain to malfunction and die,” said Cabiscol.
Statistical estimates show that one in every 10,000 people suffers from HD, translating into more than 4,000 sufferers in a country such as Spain. However, Montse Torrecilla, secretary of the Spanish Huntington’s Chorea Association (ACHE), says there is a lack of real data on the number of patients. “This is a complex issue, because one has to bear in mind the number of misdiagnoses and people who hide, or are still not aware of, their illness,” she said.
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