The principle functions of neuroinflammation are to limit tissue damage and promote
tissue repair in response to pathogens or injury. While neuroinflammation has utility,
pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology.
Understanding the mechanisms that control the three stages of inflammation (initiation,
propagation and resolution) is therefore of critical importance for developing treatments
for diseases of the central nervous system. The purinergic signaling system, involving
adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls
inflammatory responses in complex ways. Activation of the inflammasome, leading to
release of pro-inflammatory cytokines, activation and migration of microglia and altered
astroglial function are key regulators of the neuroinflammatory response. Here, we
review the role of P1 and P2 receptors in mediating these processes and examine their
contribution to disorders of the nervous system. Firstly, we give an overview of the
concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1
receptors to the underlying processes, including a discussion of cross-talk between
these different pathways. Finally, we give an overview of the current understanding
of purinergic contributions to neuroinflammation in the context of specific disorders
of the central nervous system, with special emphasis on neuropsychiatric disorders,
characterized by chronic low grade inflammation or maternal inflammation. An understanding
of the important purinergic contribution to neuroinflammation underlying neuropathology
is likely to be a necessary step towards the development of effective interventions.
