A newly discovered mechanism suggests that when stressed, neurons can eliminate the toxic protein tangles seen in Alzheimer’s
Triggering a stress response in neurons may help to unravel the damaging tangled proteins that build up in the brains of people with neurodegenerative conditions, a study carried out at the University of Cambridge has found.
The finding could lead to innovative new treatments for conditions such as Alzheimer’s and Parkinson’s, if researchers are able to identify drugs that repeat the effect, they say.
Damage is often caused to the brain tissue of patients with Alzheimer’s and Parkinson’s, due to the accumulation of misfolded proteins that break free and clump together in the brain. It was previously believed that once these protein aggregates form, it is nearly impossible to clear them.
To make their discovery, the team focused their attention on a structure found within many cells called the endoplasmic reticulum (ER). The ER produces around one-third of a cell’s proteins, allows for their movement around a cell, and can also alter them by folding.
The team initially suspected that stressing the ER by heating it to 43°C would trigger it to produce more proteins which would lead to more misfolding and greater buildups. What they found was the opposite.
“We found that stressing the cells actually eliminated the aggregation”
“Just like when we get stressed by a heavy workload, so too can cells get ‘stressed’ if they’re called upon to produce a large amount of proteins,” said Dr Edward Avezov, a researcher at the University of Cambridge and one of the authors of the study.
“We were astonished to find that stressing the cells actually eliminated the [aggregation] – not by degrading them or clearing them out, but by unravelling the aggregates, potentially allowing them to refold correctly. If we can find a way of awakening this mechanism without stressing the cells – which could cause more damage than good – then we might be able to find a way of treating some dementias,” he added.
One particular compound found to aid the unravelling was a protein called HSP, which responds to increases in heat. This understanding, Avezov said, may explain why people in Scandinavian countries who regularly use saunas may be at lower risk of developing dementia.
“One possible explanation for this is that this mild stress triggers a higher activity of HSPs, helping correct tangled proteins,” he said.
DEMENTIA IN THE UK
According to the Alzheimer’s Society, there are currently around 900,000 people in the UK living with dementia. It mainly affects people over the age of 65 but the likelihood of developing the disease increases significantly with age. Currently, around 1 in 14 people aged over 65 are living with dementia.
This rises to 1 in 6 for people aged over 80.