Memory suppressor gene may be Alzheimer's key
Experiments found knocking it out almost doubled fruit flies’ power of recall - offering hope of developing drugs that inhibit it in humans.
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Hide AdProfessor Ron Davis, of The Scripps research Institute, Florida, said: “When we knocked out this gene, the flies had a better memory, a nearly two fold better memory.
“The fact this gene is active in the same pathway as several cognitive enhancers currently used for the treatment of Alzheimer’s disease suggests it could be a potential new therapeutic target.”
While research has identified hundreds of genes required for normal memory formation, genes that suppress it are of special interest.
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Hide AdThey offer insights into how the brain prioritises and manages all of the information that it takes in every day.
These genes also provide clues for how scientists might develop new treatments for cognitive disorders such as Alzheimer’s.
The researchers identified the gene in the brain cells of Drosophila, the common fruit fly, a widely recognised substitute for human memory studies because its neurological system is very similar.
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Hide AdThe basic cell structure and composition of a fruit fly brain cell is virtually the same, although they are much fewer in number and have far fewer connections.
The study, published in the journal, Neuron screened about 3,500 Drosophila genes and identified several dozen new memory suppressors the brain has to help filter information and store only important parts. One of these, in particular, caught their attention.
When the scientists disabled this gene, known as DmSLC22A, flies’ memory of smells, the most widely studied form of memory in this model, was boosted while over expression inhibited that same memory function.
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Hide AdCo author Ze Liu, a PhD student, said: “Memory processes and the genes that make the brain proteins required for memory are evolutionarily conserved between mammals and fruit flies.
“The majority of human cognitive disease causing genes have the same functional genetic counterparts in flies.”
The gene in question belongs to a family of ‘plasma membrane transporters’, which produce proteins that move molecules, large and small, across cell walls.
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Hide AdIn the case of DmSLC22A, the new study indicates it makes a protein involved in moving neurotransmitter molecules from the connections, or synapses, between neurons back into them.
When DmSLC22A functions normally, the protein removes the neurotransmitter acetylcholine from the synapse, helping to terminate the signal.
When it is missing, more acetylcholine persists in the synapse, making the signal stronger and more persistent, leading to enhanced memory.
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Hide AdAnother of the researchers, Dr Yunchao Gai, said: “DmSLC22A serves as a bottleneck in memory formation. Considering the fact plasma transporters are ideal pharmacological targets, drugs that inhibit this protein may provide a practical way to enhance memory in individuals with memory disorders.”
Prof Davis said the next step is to develop a screen for inhibitors of this pathway that, independently or in concert with other treatments, may offer a more effective way to deal with the problems of memory loss due to Alzheimer’s and other neurodegenerative diseases.
He added: “One of the major reasons for working with the fly initially is to identify brain proteins that may be suitable targets for the development of cognitive enhancers in humans.
“Otherwise, we would be guessing in the dark as to which of the more than 23,000 human proteins might be appropriate targets.”