Specific drug targets identified in the neural circuits that encode memories could help in the treatment of brain disorders, including Alzheimer’s disease, British researchers have reported.
Researchers from the University of Bristol found specific receptors for the neurotransmitter acetylcholine. These re-route information flowing through memory circuits in the hippocampus.
Writing in Nature Communications, they say that until now, the only effective treatment for the symptoms of cognitive or memory impairment is using drugs that broadly boost acetylcholine but this leads to several side effects.
However, the discovery of the specific receptor targets means there is potential to provide the positive effects while avoiding the negative ones, they say.
Lead author Professor Jack Mellor, of the University of Bristol’s Centre for Synaptic Plasticity, said: “These findings are about the fundamental processes that occur in the brain during the encoding of memory and how they may be regulated by brain state or drugs targeting specific receptor proteins.
“In the long-term, the discovery of these specific targets opens up avenues and opportunities for the development of new treatments for the symptoms of Alzheimer’s disease and other conditions with prominent cognitive impairments.”
Dr Miles Congreve, chief scientific officer at Sosei Heptares, added: “These important studies have helped us to design and select new, exquisitely targeted therapeutic agents that mimic the effects of acetylcholine at specific muscarinic receptors, without triggering the unwanted side effects of earlier and less-well targeted treatments. This approach has the exciting potential to improve memory and cognitive function in patients with Alzheimer’s and other neurological diseases.”
Palacios-Filardo J, Udakis M, Brown G A et al. Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits. Nature Communications 16 September 2021. DOI: 10.1038/s41467-021-25280-5
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