Therapeutics: Nuclear receptor subfamily 4 group A member 2 (NURR1; NR4A2)

In vitro and rat studies suggest the antimalarial drug amodiaquine could help treat PD. In a human neuroblastoma cell-based assay of NURR1 activity, a screen of 960 drugs identified amodiaquine as an NURR1 agonist that activated the promoter of tyrosine hydroxylase (TYH) with an EC50 of 20 μM. In neurotoxin-treated primary rat neurons, amodiaquine decreased cell death compared with no treatment. In a rat model of neurotoxin-induced PD, amodiaquine decreased abnormal rotation behavior and death of TYH-positive neurons in the brain compared with vehicle. Next steps include screening and functional characterization of amodiaquine derivatives.

Acadia Pharmaceuticals Inc. has Nurr-1, an agonist of NURR1 and retinoid X receptor (RXR), in preclinical testing to treat PD. ...