Role of ROCK-associated inflammation and redox imbalance in Parkinson's disease dyskinesia: evidence from animal and patient studies.

L-DOPA-induced dyskinesia (LID) is one of the most troublesome problems in the treatment of Parkinson's disease (PD). We investigated the association of dyskinesia, inflammation and redox imbalance, and Rho kinase (ROCK) in PD using animal and patient studies. Fasudil significantly and dose-dependently improved general motor activity and dyskinesia behavior in the PD rats treated with L-DOPA. Fasudil also significantly inhibited ROCK2 expression and activity, microglial activation and proinflammatory cytokine level increase, and ameliorated redox imbalance in the substantia nigra (SN) and striatum of PD rats treated with L-DOPA. ROCK2 and SOD activity and content of TNF-α, IL-1β and MDA in the serum of PD patients with dyskinesia were significantly different from PD patients without dyskinesia. TNF-α, IL-1β and MDA content (positively) and SOD activity (negatively) were significantly associated with ROCK2 activity in the serum of PD patients with dyskinesia. Dyskinesia score was significantly associated with serum TNF-α, IL-1β and MDA content (positively), and SOD (negatively) and ROCK2 activity (positively) in the PD patients with dyskinesia. ROCK-associated inflammation and redox imbalance may participate in the pathogenesis of PD dyskinesia and ROCK inhibition could be a promising therapeutic target to improve both dyskinesia and general motor activity in PD.