A potential drug target has been discovered that could help scientists develop radical new treatments for Alzheimer’s disease. Blocking activity of the protein, known as GPR3, results in toxic deposits thought to play a key role in the disease clearing away from the brain. Laboratory mice suffering from Alzheimer’s-like symptoms showed improvements in learning, memory and social skills when they lacked GPR3, according to research published in the journal Science Translational Medicine. Further tests on the brain tissue of dead human patients indicated that when the protein is more active the disease progresses faster.
The early work shows GPR3 plays an important role in generation of beta-amyloid plaques clumps of protein fragments that build up in the brain and disrupt the function of nerve cells. Removing the protein prevented formation of new plaques in the brains of mice and cleared existing deposits away. Lead researcher Dr Amantha Thathiah, from the Flanders Institute for Biotechnology in Belgium, said: “Our research indicates that the absence of GPR3 alleviates the cognitive decline and reduces amyloid pathology in multiple disease-relevant models. “These studies identify GPR3 as a therapeutic target for AD (Alzheimer’s disease) and provide a significant level of validation necessary for the future of AD drug discovery.”Dr Clare Walton, research manager at Alzheimer’s Society, said: “With an ageing population, cases of Alzheimer’s disease will continue to rise so the need to find new treatments that can slow down or stop the disease is increasingly urgent. As it is, current treatments only help to manage some of the symptoms of Alzheimer’s and no new drugs have been discovered for more than a decade.
“Further work is needed to discover a drug that can be safely administered to target this protein. Alzheimer’s Society will spend £100 million on research over the next decade because preliminary studies like this are vital to uncover new drug targets and drive forward our search for better dementia treatments.” The research only went as far as genetically tweaking laboratory mice so they could no longer produce the protein. Developing a successful drug treatment will involve finding a molecule that interferes with GPR3’s signaling pathway. GPR3 is one of a large family of proteins that play an active role in numerous biological functions and are also linked to many diseases. Among existing drugs that target “G protein-coupled receptors” are medicines used to treat psychosis, allergies and heartburn. However finding a GPR3-targeting treatment for Alzheimer’s will not be as simple as re-purposing one of these other therapies. GPR3 belongs to a subset of “orphan” proteins whose functioning mechanism is still not fully understood. A “key” to fit the receptor’s “lock” is yet to be found.
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