Food for neuroinflammation

Inflammation is a natural protective response to potentially harmful stimuli. However, a growing corpus of evidence suggests that chronic inflammation or a disproportionate inflammatory response may be contributing and compounding factors in the genesis and development of a diverse plethora of diseases, including certain cancers, COVID-19 or Alzheimer’s Disease. In fact, in the brain, in addition to common pathological states, inflammation naturally increases as we age.

One of the most widespread pro-inflammatory signalling pathways is triggered by small endogenous metabolites known as prostaglandins. Antagonists of the EP2 receptor, a sensor for prostaglandin E2 (PGE2), have been found to reverse both the inflammatory process and its corollaries in various mouse models of brain pathologies, thus enhancing the intellectual performance of the animals.

A few synthetic compounds have been developed that potently and selectively antagonise EP2 receptor signalling. However, to the best of our knowledge, none of them has been tested in humans, presumably due to the strict regulatory requirements for progressing a new molecular entity towards clinical trials.

Encouraged by our previous and partially serendipitous success in finding molecules contained in food that modulate the activity of other receptors, we have decided to develop a similar approach in order to identify naturally-occurring EP2 antagonists.

If successful, this strategy will (1) inform us of the ideal diet in order to reduce neuroinflammation; (2) pave the way for the development of brain-oriented nutraceuticals; and (3) at a later stage guide the development of novel therapies.

So far we have built a computational model of the human EP2 receptor and we are conducting a virtual screening campaign against a pre-filtered subset of the Food Database (FooDB), which at the time of this writing contains over a hundred thousand compounds.

If you could be tempted to test a few of the most promising candidates, please, drop us a line.