Aggregated proteins – hallmark of some neurodegenerative diseases – are cleared by cell stress
A number of age-related neurodegenerative disorders are associated with the build-up of aggregated proteins, like the ones shown in yellow in this green-coloured rodent cell. The presence of tau tangles and amyloid plaques are features of Alzheimer’s disease, for example, while alpha-synuclein deposits are definitive signs of Lewy body dementia. It’s thought that such aggregates arise when the cell’s protein-folding and quality-control mechanisms no longer operate properly. And, perhaps the last thing one might expect to improve such operations would be stress. Indeed, when scientists pharmacologically stressed various cells containing aggregated proteins, they were surprised to find that the aggregates actually untangled and refolded properly – the opposite of what they were expecting. While stressing someone’s brain cells might not be a feasible treatment for neurodegeneration, this unexpected discovery suggests that further experimental tinkering with components of cellular stress pathways might yield insights into novel treatment strategies.
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