U.S. and Australian teams have elucidated the pathway that leads to microglia activation, an early step in inflammatory neurodegenerative disorders. The studies suggest that dampening microglial activity early in disease could spare nearby neurons from destruction by glial cells. The findings could breathe new life into targeting neuroinflammation as a strategy to treat disorders such as Parkinson's disease, a tactic that had fallen out of favor because of a lack of clear targets.
One study describes the anti-inflammatory role of nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1).1 The other proposes a mechanism for the proinflammatory activity of purinergic receptor P2X ligand-gated ion channel 7 (P2RX7; P2X7).2 The challenge now is connecting the dots between these targets and testing whether modulating them can protect against disease progression in animal models.
The nuclear option
Mutations in NURR1 had previously been identified as a cause of a rare hereditary form of PD.3 Based on that finding, a group at the University of California, San Diego(UCSD) sought to examine how NURR1 influenced brain inflammation triggered by bacterial endotoxins like lipopolysaccharide (LPS).
The team suspected that LPS could set off a