Preclinical study points to GPR3 as a potential target for Alzheimer's

Amantha Thathiah

Scientists and clinicians have tackled Alzheimer's disease (AD) progression from multiple angles. But two approaches have become the most accepted: halt the accumulation of toxic protein aggregates called tau tangles, or prevent beta amyloid plaques from clustering in the brain, both of which may be responsible for the deterioration of the central nervous system, leading to dementia.

Researchers at the Flanders Interuniversity Institute for Biotechnology are opting for the latter approach, saying that the loss of a protein called G protein-coupled receptor 3 (GPR3) may lower the amyloid plaque aggregation, resulting in improved cognitive function.

The team, led by Amantha Thathiah, presented its findings in the journal Science Translational Medicine earlier this week.

"We discovered that GPR3, a protein expressed in the brain, plays a significant role in the generation of amyloid-β peptides and accumulation of amyloid plaques," Thathiah said in a release. "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 and provide a significant level of validation necessary for the future of AD drug discovery."

Their therapeutic target was confirmed when they showed that when GPR3 expression is increased it correlates with disease progression in postmortem brain tissue from two cohorts of AD patients.

With a series of setbacks in the field over the past decade, this study puts another molecule in the crosshairs for AD preclinical drug development.  

- here's the release
- here's the journal article

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