Research reveals drug targets for memory enhancement

Date:
September 16, 2021
Source:
University of Bristol
Summary:
New research has identified specific drug targets within the neural
circuits that encode memories, paving the way for significant
advances in the treatment of a broad spectrum of brain disorders.



FULL STORY ========================================================================== Bristol-led research has identified specific drug targets within the
neural circuits that encode memories, paving the way for significant
advances in the treatment of a broad spectrum of brain disorders.


==========================================================================
Loss of memory is a core feature of many neurological and psychiatric
disorders including Alzheimer's disease and schizophrenia. Current
treatment options for memory loss are very limited and 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,
published in Nature Communications, identify specific receptors for
the neurotransmitter acetylcholine that re-route information flowing
through memory circuits in the hippocampus. Acetylcholine is released
in the brain during learning and is critical for the acquisition of
new memories. Until now, the only effective treatment for the symptoms
of cognitive or memory impairment seen in diseases such as Alzheimer's
is using drugs that broadly boost acetylcholine. However, this leads
to multiple adverse side effects. The discovery of specific receptor
targets that have the potential to provide the positive effects whilst
avoiding the negative ones is promising.

Lead author, Professor Jack Mellor, from 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.

The academic-industry partnership is important for these discoveries
and we hope to continue working together 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 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." "It is
fascinating how the brain prioritises different bits of information,
working out what is important to encode in memory and what can be
discarded. We know there must be mechanisms to pull out the things that
are important to us but we know very little about how these processes
work. Our future programme of work aims to reveal how the brain does
this using acetylcholine in tandem with other neurotransmitters such as dopamine, serotonin and noradrenaline," said Professor Mellor.

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Jon Palacios-Filardo, Matt Udakis, Giles A. Brown, Benjamin
G. Tehan,
Miles S. Congreve, Pradeep J. Nathan, Alastair J. H. Brown, Jack R.

Mellor. Acetylcholine prioritises direct synaptic inputs from
entorhinal cortex to CA1 by differential modulation of feedforward
inhibitory circuits. Nature Communications, 2021; 12 (1) DOI:
10.1038/s41467-021- 25280-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210916114611.htm

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