Small Molecule Originally Developed to Treat Depression Improved Memory in Alzheimer’s Mouse Study

Small Molecule Originally Developed to Treat Depression Improved Memory in Alzheimer’s Mouse Study
A small molecule delivered orally for 56 days improved memory in mice carrying the ApoE4 gene, the most common genetic risk factor for Alzheimer’s disease. The molecule, called A03 and initially developed as a candidate therapy for depression, increased the levels of a protective protein, called sirtuin 1, in the hippocampus — a brain region involved in memory formation. The study with those findsings, “A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer’s disease mouse model,” was published in Scientific Reports. The apolipoprotein E4 (ApoE4) gene is the major known genetic risk factor for sporadic Alzheimer’s disease, present in about two of three people with the disease. This gene is linked with accumulation of the amyloid-beta protein, one of the hallmarks of Alzheimer’s disease. Previous studies have shown that expression of ApoE4 significantly reduces the levels of sirtuin 1 (SirT1), a protein known for its neuroprotective effects. Low SirT1 levels trigger the death of nerve cells by promoting the toxic accumulation of amyloid-beta and tau protein, another protein linked with Alzheimer’s disease and related dementias. One particular study showed that restoring SirT1 levels back to normal reduced the damaging effects of tau accumulation. Researchers fr
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