Neuroprotective effects of pramipexole transdermal patch in the MPTP-induced mouse model of Parkinson's disease

Abstract

Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons. To avoid inconvenience of frequent administration caused by short half life and recurrence of symptoms such as tremor and bradykinesia incurred by drug elimination, a novel long-acting pramipexole transdermal patch has been made. In the present study, we evaluated the neuroprotective effects and underlying mechanisms of pramipexole patch (PPX patch) in a subacute PD mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PPX patch treatment improved dyskinesia. MPTP-induced reduction of DA as well as its metabolites DOPAC and HVA in the striatum were prevented by PPX patch in a dose-dependent manner. PPX patch also restored the activity of antioxidant enzymes including SOD, GSH-Px and CAT in the striatum while reduced the content of MDA. Furthermore, PPX patch upregulated Nrf2/HO-1 expression. The protective effects of PPX patch was also associated with downregulation of the Bax/Bcl-2 ratio and Apaf-1, inhibition of cytochrome c release and inactivation of caspase-9 and caspase-3. In conclusion, our studies demonstrated that the long-acting pramipexole patch exerts its neuroprotective effects, at least in part, by inhibiting oxidative stress and mitochondrial apoptosis pathway and holds promise as a candidate drug.

Pramipexole prevents ischemic cell death via mitochondrial pathways in ischemic stroke

“…Mechanistically, PPX promoted a reduction in mitochondrial ROS, which could be one of the possible explanations for these findings. Many studies support the anti-oxidative nature of PPX (Sayeed et al, 2006; Wang et al, 2018). Thus, it can be concluded that the anti-oxidative property of PPX could promote recovery in mitochondrial respiration after ischemia.…”

Nrf2/HO-1 mediates neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury

“…Post-treatment with PPX reduced the release of cyt-c by attenuating the mitochondrial damage. Previous studies have demonstrated that PPX inhibits cyt-c leakage in different cell lines and in vivo ( Shin et al, 2007 ; Wang et al, 2018 ). Based on the present results, we can conclude that PPX treatment protects mitochondria by multiple pathways in TBI.…”

“…Few studies have demonstrated the relationship between PPX and Nrf2 following brain injury. Recently, Wang et al (2018) reported that PPX administration increased the expression of Nrf2 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease. However, the molecular mechanism underlying the effects of PPX in TBI is poorly understood.…”

Pramipexole Reduces zif-268 mRNA Expression in Brain Structures involved in the Generation of Harmaline-Induced Tremor

“…it inhibits mitochondrial permeability transition pores, when given in nanomolar concentrations, by binding to the inner side of the mitochondrial membrane [43]. Mitochondrial mechanisms have been suggested to underlie antioxidant, antiapoptotic, neuroprotective efficiency of pramipexole which is visible already after its low doses [44,45]. It is currently unknown whether such non-dopaminergic mechanism indeed contributes also to the inhibitory influence of pramipexole on harmaline effects described in the present study and earlier [5] and to the tremorolytic effects of this drug in ET [21].…”