French government price for Pr Dulce Papy-Garcia

One year extension

ArrestAD project was initially scheduled to last 4 years (2017-2020), however, due to 1) COVID-19 sanitary crisis, 2) delay in tasks that required animals’ strains and human cells and 3) SCell termination, the consortium requested an amendment with no change to the maximum EU contribution to extend project duration until December 31st, 2021 (M60).

An improved brace of sulfations

After preprinting our two papers (here and here) on inhibitors of sulfotransferases they were submitted to Biochem J. The referees made some excellent suggestions – a bit of work, but the extra controls add even more certainty, which is never a bad thing.

The papers are published back to back.  The Biochemical Journal recognised the fundamental importance of the papers in opening up a new area of signalling  with an accompanying editorial by Sharon Yeoh and Richard Bayliss, as well as the issue cover.

Our papers describe the first high throughput assays for sulfotransferases, the enzymes that transfer sulfate from PAPS to their substrates. These assays were developed in parallel for three Golgi sulfotransferases; the two tyrosyl protein sulfotransferases, which sulfate selected tyrosines on proteins, and heparan sulfate sulfotransferase 2, one of the polysaccharide sulfotransferases responsible for the sulfation of heparanosan, and so producing the protein binding sites in the heparan sulfate product. Heparan sulfate has long been known to be associated with Alzheimer’s Disease

More recently, heparan sulfate with an unusual sulfation pattern has been shown to accumulate in neurons in experimental models of Alzheimer’s Disease and so to drive the formation of Tau fibrils, which is integral to the Taupathy seen in Alzheimer’s disease. The development of screens for inhibitors of thee enzymes described in our two papers also demonstrates that PAPS competitors can inhibit sulfotransferases selectively. At the very least this will allow a chemical biology approach essential to elucidate the relationship between heparan sulfate and Tau fibrillation in cells and so establish the structure-function underpinnings of a longstanding molecular pathology of Alzheimer’s Disease.