Study Pinpoints New Drug Target for Alzheimer's Disease

JUNE 16, 2014
Jacquelyn Gray

After several once-promising drugs failed to treat Alzheimer’s disease in clinical trials, researchers at Penn State University claim to have found a new target for future treatments.

“Billions of dollars were invested in years of research leading up to the clinical trials of those Alzheimer's drugs, but they failed the test after they unexpectedly worsened the patients' symptoms," lead study author Gong Chen, said in a statement.

According to Chen, many unsuccessful drugs for Alzheimer’s disease targeted brain plaque caused by an excess of amyloid proteins, which can cause death in brain neurons. In the May 2014 issue of Nature Communications, Chen and his co-investigators instead focused on gamma-aminobutyric acid (GABA), a neurotransmitter present in deformed cells called "reactive astrocytes” that are located in the entry to the hippocampus, which is integral for memory and learning.

For their study, the investigators aimed to construct neurotransmitter detection models in both healthy and affected mice. In doing so, the researchers found a high concentration of GABA correlated with poor memory and learning performance. Additionally, they discovered an astrocyte-specific GABA transporter that controls the presence of GABA neurotransmitters.

Based on their findings, the authors claimed this location could be a promising new target for future Alzheimer’s disease drugs, though they cautioned that over-inhibiting the GABA neurotransmitter could slow down neurons in the gateway to the hippocampus known as the dentate gyrus, thus negatively affecting learning and memory abilities. Nevertheless, the researchers noted a high concentration of GABA could be used as a biomarker for the disease.

 “Our studies suggest that reducing the excessive GABA inhibition to the neurons in the brain's dentate gyrus may lead to a novel therapy for Alzheimer's disease,” Chen commented.  “An ultimate successful therapy may be a cocktail of compounds acting on several drug targets simultaneously.”

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