Neuroinflammation
Inflammation within the central nervous system, involving activation of microglia and astrocytes. Chronic neuroinflammation contributes to neurodegeneration. Trofinetide's mechanism in Rett syndrome involves modulating neuroinflammation and supporting synaptic function.
Technical Context
Neuroinflammation involves activation of resident CNS immune cells: microglia (the brain's macrophages, existing in M1 pro-inflammatory and M2 anti-inflammatory phenotypes) and astrocytes (reactive astrocytes proliferate and form glial scars). Acute neuroinflammation is protective (clearing debris, fighting infection), but chronic neuroinflammation contributes to neurodegeneration through: sustained release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), reactive oxygen/nitrogen species production, complement activation, and blood-brain barrier disruption. Trofinetide (GPE) modulates neuroinflammation in Rett syndrome — proposed mechanisms include: reducing microglial activation, modulating astrocyte reactivity, and normalising glutamate neurotransmission. Glatiramer acetate modulates immune responses in multiple sclerosis by shifting T cell populations from pro-inflammatory Th1/Th17 to anti-inflammatory Th2/Treg phenotypes, indirectly reducing CNS inflammation.