VDA Agonist Neuroprotection via AKT Pathway in MPTP Pre-clinical Model of Parkinson's

Antiparkinsonian agents that are direct dopamine (DA) agonists, such pramipexole, have shown to be neuroprotective against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage to the DA system in mice. The importance of identifying the neuroprotective capabilities of DA agonists has been underscored by the recent publication determining that percentage decline in BCIT uptake to the dopamine transporter (DAT) was less in Parkinson's disease (PD) patients on pramipexole as compared to those on levodopa therapy. The mechanisms by which direct DA agonists may provide neuroprotection remain unproven. We will explore if proteins known to regulate 'death signal' pathways in dopamine neurons are regulated by pramipexole. Understanding the signaling pathways involved in neuroprotection by DA agonists will allow the design of drugs for selective therapeutic targets in PD.