The parthenolide derivative ACT001 synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson's disease in mice.

The parthenolide derivative ACT001 synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson's disease in mice. Behav Brain Res. 2019 Nov 04;:112337 Authors: Liu Q, Zhang S, Zhu D, Tang X, Che Y, Feng X Abstract L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the main drug used to treat Parkinson's disease (PD). However, long-term use of L-DOPA causes substantial side effects, and we hope to find a biological active ingredient that synergizes with a low-dose of L-DOPA to achieve the same therapeutic effect as that of a high-dose of L-DOPA. The natural product parthenolide (PTL) is the active ingredient in the medicinal plant feverfew (Tanacetum parthenium) and has antioxidant and anti-inflammatory properties. ACT001, a fumarate salt form of dimethylaminomicheliolide (DMAMCL), is a derivative of parthenolide and has comparable effects to those of PTL but exhibits higher stability in the plasma and is available at a lower cost. In our study, we used ACT001 in combination with L-DOPA to treat 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice. Specifically, ACT001 significantly reduced motor dysfunction and dopaminergic neurodegeneration in MPTP-treated mice. Furthermore, ACT001 abolished MPTP-induced α-synuclein overexpression, astrocyte activation and interleukin-1β (IL-1β) production in the substantia nigra and striatum of the mouse brain. In addition, ACT001 increased the lev...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research