Co-Application of C16 and Ang-1 Improves the Effects of Levodopa in Parkinson Disease Treatment.

BACKGROUND

Levodopa is regarded as a standard medication in Parkinson disease (PD) treatment. However, long-term administration of levodopa leads to levodopa-induced dyskinesia (LID), which can markedly affect patient quality of life. Previous studies have shown that neuroinflammation in the brain plays a role in LID and increases potential neuroinflammatory mediators associated with the side effects of levodopa.

OBJECTIVE

The treatment effect of C16 (a peptide that competitively binds integrin αvβ3 and inhibits inflammatory cell infiltration) and angiopoietin-1 (Ang-1; a vascular endothelial growth factor vital for blood vessel protection), along with levodopa, was evaluated in a rodent model of PD.

METHODS

We administered a combination of C16 and Ang-1 in a rodent model of PD induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Seventy-five mice were randomly divided into five treatment groups: control, vehicle, levodopa, C16+Ang-1, and levodopa+C16+Ang-1. Behavioral, histological, and electrophysiological experiments were used to determine neuron function and recovery.

RESULTS

The results showed that C16+Ang-1 treatment alleviated neuroinflammation in the CNS and promoted the recovery effects of levodopa on neural function.

CONCLUSION

Our study suggests that C16+Ang-1 can compensate for the shortcomings of levodopa, improve the CNS microenvironment, and ameliorate the effects of levodopa. This treatment strategy could be developed as a combinatorial therapeutic in the future.