P2X7 Receptors as a Transducer in the Co-Occurrence of NeurologicalPsychiatric and Cardiovascular Disorders : A Hypothesis

Abstract EN

Background.

Over-stimulation of the purinergic P2X7 receptor may bring about cellular dysfunction and injury in settings of neurodegeneration, chronic inflammation, as well as in psychiatric and cardiovascular diseases.

Here we speculate how P2X7 receptor over-activation may lead to the co-occurrence of neurological and psychiatric disorders with cardiovascular disorders.

Presentation.

We hypothesize that proinflammatory cytokines, in particular interleukin-1β, are key players in the pathophysiology of neurological, psychiatric, and cardiovascular diseases.

Critically, this premise is based on a role for the P2X7 receptor in triggering a rise in these cytokines.

Given the broad distribution of P2X7 receptors in nervous, immune, and vascular tissue cells, this receptor is proposed as central in linking the nervous, immune, and cardiovascular systems.

Testing.

Investigate, retrospectively, whether a bidirectional link can be established between illnesses with a proinflammatory component (e.g., inflammatory and chronic neuropathic pain) and cardiovascular disease, for example, hypertension, and whether patients treated with anti-inflammatory drugs have a lower incidence of disease complications.

Positive outcome would indicate a prospective study to evaluate therapeutic efficacy of P2X7 receptor antagonists.

Implications.

It should be stressed that sufficient direct evidence does not exist at present supporting our hypothesis.

However, a positive outcome would encourage the further development of P2X7 receptor antagonists and their application to limit the co-occurrence of neurological, psychiatric, and cardiovascular disorders.