1. β‑Lapachone ameliorates L‑DOPA‑induced dyskinesia in a 6‑OHDA‑induced mouse model of Parkinson's disease
- Author
-
Lee In-Bok, Hye-Yeon Park, Young-Keun Choi, Kyoung-Shim Kim, Chul-Ho Lee, Young-Kyoung Ryu, and Jun Go
- Subjects
Male ,Cancer Research ,astrocyte activation ,Parkinson's disease ,Substantia nigra ,Striatum ,Pharmacology ,Biochemistry ,Levodopa ,Mice ,GSK-3 ,Dopamine ,β-Lapachone ,Genetics ,Animals ,Medicine ,Parkinson Disease, Secondary ,Oxidopamine ,Molecular Biology ,Dyskinesias ,business.industry ,Articles ,medicine.disease ,Abnormal involuntary movement ,3,4-dihydroxyphenyl-l-alanine-induced dyskinesia ,nervous system diseases ,glycogen synthase kinase 3β ,Oncology ,Dyskinesia ,Apoptosis ,Molecular Medicine ,medicine.symptom ,business ,Naphthoquinones ,medicine.drug - Abstract
The dopamine precursor 3,4-dihydroxyphenyl- l-alanine (L-DOPA) is the most widely used symptomatic treatment for Parkinson's disease (PD); however, its prolonged use is associated with L-DOPA-induced dyskinesia in more than half of patients after 10 years of treatment. The present study investigated whether co-treatment with β-Lapachone, a natural compound, and L-DOPA has protective effects in a 6-hydroxydopamine (6-OHDA)-induced mouse model of PD. Unilateral 6-OHDA-lesioned mice were treated with vehicle or β-Lapachone (10 mg/kg/day) and L-DOPA for 11 days. Abnormal involuntary movements (AIMs) were scored on days 5 and 10. β-Lapachone (10 mg/kg) co-treatment with L-DOPA decreased the AIMs score on both days 5 and 10. β-Lapachone was demonstrated to have a beneficial effect on the axial and limb AIMs scores on day 10. There was no significant suppression in dopamine D1 receptor-related and ERK1/2 signaling in the DA-denervated striatum by β-Lapachone-cotreatment with L-DOPA. Notably, β-Lapachone-cotreatment with L-DOPA increased phosphorylation at the Ser9 site of glycogen synthase kinase 3β (GSK-3β), indicating suppression of GSK-3β activity in both the unlesioned and 6-OHDA-lesioned striata. In addition, astrocyte activation was markedly suppressed by β-Lapachone-cotreatment with L-DOPA in the striatum and substantia nigra of the unilateral 6-OHDA model. These findings suggest that β-Lapachone cotreatment with L-DOPA therapy may have therapeutic potential for the suppression or management of the development of L-DOPA-induced dyskinesia in patients with PD.
- Published
- 2021