This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease - has been proposed.
- Michele Vendruscolo
Academics at the University of Cambridge and at Lund University in Sweden have devised the first strategy to ‘go after’ the cause of the devastating disease, which could eventually lead to the development of new drugs to treat dementia. Their findings are reported in the journal PNAS.
“This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease - has been proposed,” said Professor Michele Vendruscolo from Cambridge’s Department of Chemistry, the paper’s senior author. “Until very recently scientists couldn’t agree on what the cause was so we didn’t have a target. As the pathogens have now been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to aim drugs at these toxic particles.”
Alzheimer’s disease leads to the death of nerve cells and tissue loss throughout the brain. Over time, the brain shrinks dramatically and the cell destruction causes memory failure, personality changes, and problems carrying out daily activities.
Scientists identified abnormal deposits called protein oligomers as the most likely suspects of the cause of dementia. Although proteins are normally responsible for important cell processes, when people have Alzheimer’s disease these proteins become rogue, form clumps and kill healthy nerve cells.
“A healthy brain has a quality control system that effectively disposes of potentially dangerous masses of proteins, known as aggregates,” said Vendruscolo. “As we age, the brain becomes less able to get rid of the dangerous deposits, leading to disease. It is like a household recycling system, if you have an efficient system in place then the clutter gets disposed of in a timely manner. If not, over time, you slowly but steadily accumulate junk that you don’t need. It is the same in the brain.”
The research was carried out by an international team of scientists that also included Professor Sir Christopher Dobson, Master of St John's College, University of Cambridge, at the Centre for Misfolding Diseases (CMD), which he co-founded. “This interdisciplinary study shows that it is possible not just to find compounds that target the toxic oligomers that give rise to neurodegenerative disorders but also to increase their potency in a rational manner,” he said. “It now makes it possible to design molecules that have specific effects on the various stages of disorders such as Alzheimer’s disease, and hopefully to convert them into drugs that can be used in a clinical environment.”
Image: Conceptual image showing blurred brain with loss of neuronal networks
Credit: Kateryna Kon
Reproduced courtesy of the University of Cambridge