Research highlight

Alzheimer’s disease just a sweet memory?

Nature Chemical Biology

February 27, 2012

Using an enzyme inhibitor to keep sugar groups on the protein tau in place, could potentially open new treatment options for Alzheimer’s disease, reports a new study published this week in Nature Chemical Biology. This research thus provides insights into the inner workings of an aspect of the disease, offering new opportunities for treatment. Alzheimer’s disease is characterized by memory loss and mental confusion. At the cellular level, aggregation of the protein tau into larger fibrils is a defining feature of the disease. Many scientists hoping to treat the disease focus on finding molecules that interact directly with these fibrils to break them apart or slow their formation. However, it remains unclear what controls their formation; if these earlier controlling elements could be identified, early intervention to slow or prevent disease development may be possible. David Vocadlo and colleagues show that treatment of transgenic mice predisposed to develop Alzheimer’s disease with Thiamet-G, an inhibitor of the enzyme O-GlcNAcase, slows formation of disease-associated aggregates and decrease neuronal cell loss. In particular, the inhibitor prevents the enzyme from removing sugar groups from tau; in vitro assays confirm these sugar groups work directly to slow fibril formation.

doi: 10.1038/nchembio.797

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