Pramipexole improves mitochondrial function in aβ42 induced transgenic ad model of drosophila melanogaster

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disorder with typical clinical interventions characterized by loss of memory and cognitive function. Several lines of evidence strongly implicate mitochondrial dysfunction as a major causative factor in AD, although the molecular mechanisms responsible for mitochondrial dysfunction in AD are poorly understood. Pramipexole is a dopamine agonist with proven efficacy in mitochondrial mediated neuroprotective effect. Considering this property, we examined the effect of pramipexole in AD. To gain insight into the molecular mechanism responsible for the pathogenesis of AD, we have choosen UAS/GAL4 system for the development of transgenic AD flies that overexpress Aβ42 in the brain of Drosophila. The symptoms such as reduced lifespan, locomotor defects, and memory impairment, mitochondrial membrane potential, oxygen consumption of mitochondria and expression of caspase 3 along with mitogen associated protein kinases linked with AD were determined in the presence of pramipexole. Pramipexole resisted the Aβ42 induced behavioral outcomes, mitochondrial membrane potential, oxygen consumption along with expression of apoptotic factors (ERK, p38, pJNK and caspase 3). Thus the present study could be beneficial to find out the role of pramipexole in transgenic AD flies overexpressing human Aβ42.