We report for the first time that Nedd4-2 knockdown ameliorates movement disorders in PD mice and increases tyrosine hydroxylase expression in the midbrain and striatum of PD mice; Nedd4-2 knockdown also attenuates astrogliosis and reactive microgliosis in the MPTP model that may be associated with glutamate excitotoxicity. This evidence concerns the gene NEDD4L and Parkinson disease.