Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015)
Funder: NRDIO
(Open access funding provided by Semmelweis University)
Immune activation in the prenatal and early postnatal periods is increasingly implicated
in the aetiology of neurodevelopmental disorders, such as autism spectrum disorder
and schizophrenia, by disrupting critical neurodevelopmental processes. The impact
of immune activation on brain development can be influenced by the type, timing, location,
and severity of the infection. Viral, bacterial, and parasitic infections, as well
as maternal autoimmune diseases, can lead to the activation of the purinergic P2X7
receptors, thereby contributing to neuroinflammation. Upon activation, P2X7 induces
the assembly of the NLRP3 inflammasome, leading to the release of the pro-inflammatory
cytokine IL-1β. Besides activation of additional inflammatory mediators, excessive
IL-1β during critical periods of brain development can disrupt neuronal migration,
synapse formation, dendritic morphology and blood-brain barrier integrity, contributing
to a range of neurodevelopmental abnormalities. Animal studies have shown that inhibiting
the components of the P2X7/NLRP3/IL-1β pathway can mitigate these adverse effects.
This review examines the role of the P2X7/NLRP3/IL-1β pathway in mediating the effects
of infection and neuronal inflammation on brain development. We discuss the therapeutic
potential of targeting this pathway with a balanced approach that reduces long-term
neuronal inflammation while preserving essential immune functions.
