A new link has been identified between short-term memory and a protein called beta-arrestin that could blaze a new path toward the therapeutic treatment of neurological disorders, especially Alzheimer’s disease. The discovery was made by biomedical scientists at the University of California, Riverside.
This is the first study that has linked beta-arrestin to Alzheimer’s and learning and memory.
Beta-arrestin is expressed in various cells of the body, including the hippocampus, an area of the brain connected to learning and the formation of short-term memories. Beta-arrestin is one of many “scaffolding proteins”—proteins that support neuron connections. The absence of beta-arrestin has been shown to impair normal learning in mice.
In the hippocampus, new connections called synapses continue to form between neurons. When the brain learns something new, connections are formed and some old ones are strengthened through a process known as long-term potentiation (LTP).
However, since brains have only a limited capacity, other old connections must disassemble through a process called long-term depression (LTD) in order for new synapses to form.
Beta-arrestin ensures the plasticity of synaptic connections and LTD by regulating the “actin cytoskeleton,” a network of proteins that shapes the “backbone” of neurons and helps form new synaptic connections and disassembles old ones.
“In some pathological conditions such as Alzheimer’s disease, loss of the old synaptic connections far exceeds the formation of new ones, resulting in overall loss of synapses and short-term memory loss,” said Iryna M. Ethell, an associate professor of biomedical sciences and the lead author of the research paper.
“Our work, done on mice, shows that if beta-arrestin is removed from neurons, this loss of synapses is prevented. But we also know that beta-arrestin is required for normal learning and memory; so a fine balance needs to be established. This balance could be easily achieved by pharmaceutical drugs in the future.”
Beta-arrestin can be visualized as energy given to a puppeteer (actin cytoskeleton) who controls the strings of a puppet (interneuronal connection), explains Ethell. In order for a person to learn something, the puppeteer needs to move the strings in a specific order.
However, in patients with Alzheimer’s, this energy supply overactivates and the strings are pulled in a disorderly fashion that results in the strings being broken (loss of synapses) and the puppets collapsing. Although the removal of beta-arrestin would avoid this collapse, a complete loss of the protein would result in no movement of the puppets at all (no learning in the brain).
“A selective tuning of beta-arrestin activity is therefore necessary to partially reduce synapse disassembly,” said Crystal G. Pontrello, the first author of the research paper and a postdoctoral researcher in Ethell’s lab. “What you want, ideally, is the elimination of only some unused old synaptic connections so that there is room to make new connections.”
The research is published in the Proceedings of the National Academy of Sciences.