Medical Research Council - London Institute of Medical Sciences

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Lost in Translation
29 March 2018

Lost in Translation

Billions of times a day chemical instructions in our genes are translated into proteins – tiny machines that work away in our cells before being broken down and recycled by proteasomes. It’s a beautiful, neat process – but it goes awry in neurodegenerative diseases. Faulty genes can disrupt healthy translation, producing sprawling protein clumps called aggregates, which clog up life inside cells. This computer model is based on 3D cryo-electron tomography of a single aggregate in a neuron. The aggregate’s red ribbon-like curls scoop up and disable the green-coloured proteasomes, leaving neurons unable to break down old or faulty proteins – a hallmark of amyotrophic lateral sclerosis. Different aggregates may create different problems – another type forms hard spindles which leave proteasomes alone, but damage the endoplasmic reticulum, potentially causing the symptoms of Huntington’s disease. Studying these differences helps researchers understand how aggregates work, with a view to blasting them apart with drugs.

Written by John Ankers

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