A new University of Bristol-led research has identified specific drug targets within the neural circuits that encode memories and pave the way for significant advances in treating a broad spectrum of brain disorders.
Loss of memory is a core feature of the many neurological and psychiatric disorders and Alzheimer’s illness, and schizophrenia.
Current treatment choices for the cognitive state are minimal, and therefore the search for safe and effective drug therapies has, until now, had limited success.
The research was done in collaboration with colleagues at the international biopharmaceutical company Sosei Heptares.
The findings, revealed in Nature Communications, establish specific receptors for the neurotransmitter acetylcholine that re-route information flowing through memory circuits within the hippocampus.
A neurotransmitter is discharged in the brain during learning and is vital for the acquisition of new memories. Until now, the only effective treatment for cognitive or memory impairment symptoms seen in diseases like Alzheimer’s is using drugs that broadly boost acetylcholine. However, this ends up in multiple adverse aspect effects.
The discovery of specific receptor targets that can supply positive outcomes while avoiding negative ones is promising.
Lead author, professor Jack Mellor, from the University of Bristol’s Centre for synaptic plasticity, said: “These findings are regarding the fundamental processes that occur in the brain throughout the encoding of memory and how they will be regulated by brain state or drugs targeting specific receptor proteins.
In the long term, discovering these specific targets opens up avenues and opportunities for developing new treatments for the symptoms of Alzheimer’s and other conditions with distinguished cognitive impairments.
The academic-industry partnership is essential for these discoveries, and that we hope to continue operating along on these projects.”
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 consequences of acetylcholine at specific muscarinic receptors, while not triggering the unwanted side effects of earlier and less-well targeted treatments.
This approach has the exciting potential to enhance memory and cognitive perform in patients with Alzheimers and other neurological diseases.”
“It is fascinating how the brain prioritises totally different bits of knowledge, figuring out what’s necessary to encode in memory and what can be discarded. we all know there must be mechanisms to tug out the things that are necessary to us however we all know little or no regarding how these processes work.
Our future programme of work aims to reveal how the brain work using acetylcholine in tandem with alternative neurotransmitters like dopamine, serotonin and noradrenaline,” said academician Mellor.
The University of Bristol’s Centre for synaptic plasticity
The Centre for synaptic plasticity started as a venture between the Medical Research Council and the University of Bristol. Research is directed towards understanding synaptic plasticity in each standard and disease state, like epilepsy.
Work inside the Centre is allotted in a multidisciplinary and cooperative manner, with different research teams endeavour various aspects of a specific question.
Based inside the college of Medical Sciences and the Dorothy Hodgkin Building, teams inside the Centre enjoy a recently refurbished research atmosphere with access to state-of-the-art facilities and equipment.
The team behind this research is based within the University of Bristol’s Centre for synaptic plasticity under the umbrella of the school of Physiology, pharmacology & neuroscience and bristol neuroscience, and the project was a collaboration with researchers at Sosei Heptares.
