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

Abstract

Xiao-Xiao Fu,1,* Jin Wang,1,* Hua-Ying Cai,1 Hong Jiang,1 Jin-Zhan Jiang,2 Hao-Hao Chen,2 Shu Han1 1Institute of Anatomy and Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, People’s Republic of China; 2Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu Han, Institute of Anatomy, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, 866 Yuhangtang Road, Hangzhou, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected] Hao-Hao Chen, Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, 1188 Wuzhou Steet, Jinhua, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: 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 αvβ 3 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.Keywords: levodopa-induced dyskinesia, Parkinson’s disease, C16+Ang-1 treatment, neuroinflammation, microenvironment

Keywords

• levodopa-induced dyskinesia
• parkinson’s disease
• c16+ang-1 treatment
• neuroinflammation
• microenvironment