Nerve signals protect cells under oxidative stress

Oxidative stress occurs when cells produce more damaging molecules (reactive oxygen species, or ROS) than they can neutralise. It plays a role in ageing and in neurodegenerative diseases. Until now, it was unclear how the body coordinates that response as a whole, beyond what individual cells can handle on their own.

In the model organism Caenorhabditis elegans (a small roundworm widely used in ageing research), the researchers found that acetylcholine, a neurotransmitter used by nerve cells to communicate, plays a crucial role in protecting the whole organism. Worms lacking acetylcholine were substantially more vulnerable to sustained oxidative stress than normal worms.

A muscarinic receptor as the switch

The team identified a specific receptor: GAR-3, a muscarinic acetylcholine receptor (a type of receptor on cell surfaces that picks up the acetylcholine signal). When that receptor was non-functional, worms failed to scale up their protein degradation processes under stress. The proteasome (the cellular system that clears damaged proteins) was not activated. That link proved critical: without increased protein turnover, damaged proteins accumulate and the cell becomes more vulnerable.

When the researchers overexpressed GAR-3 in motor neurons, the worms survived longer under chronic oxidative stress.

Connection to neurodegenerative disease

The study, published in eLife, draws a connection between disrupted cholinergic signalling and increased vulnerability to oxidative damage. That is relevant to neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease, where cholinergic signal loss and oxidative stress both play a role. The findings are preliminary and limited to an animal model, but they offer a concrete target for further research into how the nervous system coordinates cellular repair.

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