Medical Research Council - London Institute of Medical Sciences

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Slow Traffic

Insight into the signals involved in axonal transport - the movement of molecules along motor neurons - disrupted in ALS

26 February 2023

Slow Traffic

For neurons to survive and function, they need good communication between the nucleus in the cell body, and distant nerve endings. To achieve this, motor proteins move molecules along cytoskeletal filaments, in compartments called signalling endosomes. Yet this axonal transport is often disrupted in motor neuron diseases like amyotrophic lateral sclerosis (ALS), characterised by gradual destruction of motor neurons and muscle atrophy. Mice with ALS symptoms show impaired axonal transport specifically in fast motor neurons, those preferentially degraded in ALS: they become unresponsive to stimulation by BDNF, a growth factor that normally speeds up endosome traffic, and the balance between different BDNF receptors is altered in the muscles they innervate. Higher levels of some receptor types (like p75NTR, pictured in purple at a neuromuscular junction, where neurons and muscles connect) could potentially interfere with other BDNF-dependent pathways. Investigating these disruptions will help better understand the mechanisms behind this devastating disease.

Written by Emmanuelle Briolat

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