Suppression of Neurodegeneration in the Drosophila Models of Human Neurodegenerative Disorders

Abstract

Our lab has previously identified a mutation (levy) that provides a model of Leigh Syndrome (LS) in Drosophila melanogaster, as well as a second mutation, named Su(levy), which suppresses levy induced neurodegeneration (ND). The Su(levy) mutation confers resistance to temperature‐induced‐paralysis, a phenotypic marker of levy in Drosophila. Experiments are underway to identify and characterize which gene the suppressor mutation resides within. Preliminary experiments suggest that ND in the levy mutant may be caused by oxidative stress, a feature common to many neurodegenerative disorders such as Parkinson's Disease (PD) and Alzheimer's Disease (AD). This fact has broadened the suppressor mutation's application to possibly include PD and AD. The pesticide rotenone is known to induce Parkinson's‐like symptoms in humans and flies. Using rotenone to create a PD model, our lab is testing whether the suppressor can alleviate the phenotypic symptoms of this model. The suppressor mutation is being genetically combined with AD and PD mutations to further assess its ability to alleviate locomotor symptoms in the fly models of these disorders. The Su(levy) mutation made the levy flies resistant to paralysis. Experiments in progress suggest that the Su(levy) mutation may protect flies from the effect of the pesticide rotenone on locomotion. Suppressor's effects on PD and AD mutants will be measured through longevity, locomotion, and measurement of oxidative stress through ROS assays. If suppressor can alleviate ND in these models, this could provide leads to developing therapeutic approaches toward multiple neurodegenerative disorders. Funded by grant 1R03NS063148–01 from NINDS.