Discovering a potential new treatment for Huntington's disease, researchers have found that normal synaptic activity in nerve cells protects the brain from the misfolded proteins characteristic to the ailment.
Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego conducted the new study.
AdvertisementOn the other hand, excessive extrasynaptic activity (aberrant electrical activity in the brain, usually not associated with communication between nerve cells) enhances the misfolded proteins' deadly effects.
Researchers also found that the drug Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity.
Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein.
The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins.
However, excessive extrasynaptic activity contributed to increased nerve cell death.
The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity.
"Chronic neurodegenerative diseases like Huntington's, Alzheimer's and Parkinson's are all related to protein misfolding. We show here, for the first time, that electrical activity controls protein folding, and if you have a drug that can adjust the electrical activity to the correct levels, you can protect against misfolding," Nature quoted study leader Dr. Stuart A. Lipton.
"Also, this verifies that appropriate electrical activity is protective, supporting the 'use it or lose it theory' of brain activity at the molecular level. For example, this finding may explain why epidemiologists have found that 'using' your brain by performing crossword puzzles and other games can stave off cognitive decline in diseases like Alzheimer's," he added.
The research was published in the journal Nature Medicine.
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