Brain ‘trick’ offers treatment hope for Alzheimer’s

An ageing population means that neurodegeneration, such as Alzheimer’s disease, is one of the major health problems in the developed world. But researchers at the University of York and Simon Fraser University in Burnaby, British Columbia, have designed an enzyme inhibitor which could ‘trick’ the brain and so help to halt neurodegeneration.

The research is published in the latest issue of Nature Chemical Biology.

One of the causes of neurodegeneration is a modification to the protein ‘tau’, which helps to maintain the stability of neurones in the brain, causing them to form aggregates termed ‘tangles’.

These diseases, or ‘tauopathies’ are believed to be caused by a form of the protein tau which has been excessively modified with phosphate.

By studying the chemistry and structure of relevant enzymes, the research teams at York, led by Professor Gideon Davies, and Simon Fraser, led by Professor David Vocadlo, have designed an enzyme inhibitor that prevents the phosphorylation of tau in animal models. They have effectively tricked the brain’s own enzymes into installing a sugar on to tau in place of the detrimental phosphates.

The enzyme inhibitor, termed a ‘thiazoline’, developed by Professor Vocadlo and Professor Davies is not yet a drug, but it is a major breakthrough in finding compounds that cross the blood-brain barrier to elicit beneficial effects that prevent the onset of tauopathies.

Professor Davies, of the Department of Chemistry at York, said: “We hope that the work will evolve into new drugs to treat Alzheimer’s disease, although that is still many years off. The work highlights the synergy of studying the chemistry of enzymes in living cells.”

The York /Simon Fraser collaboration also revealed the first structure of the enzyme responsible for the installation of these protective sugars in a paper in Nature Structural & Molecular Biology earlier this month.