MDS 17th International Congress of Parkinson's Disease and Movement Disorders, Volume 28, June 2013 Abstract SupplementMovement Disorders 2013Sydney, Australia June 16-20, 2013.

http://www.mdsabstracts.com/abstract.asp?MeetingID=798&id=107223

Omi-mediated detoxification of α-synuclein-induced neurotoxicity in a drosophila model of Parkinson's disease

Rahman ,  M.M., Akhter ,  S., Islam ,  M.S., Kim ,  H.J., Hong ,  S.T.

Jeonju-si, Korea

Objective: To investigate the neuroprotective role of Drosophila Omi (dOmi) in Parkinson's disease (PD) in vivo.

Background: Parkinson's disease is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and abnormal accumulation of α-synuclein (α-syn) into aggregates called Lewy bodies. Recently, Omi has been linked to PD pathogenesis and cellular protein quality control system. Omi is a mitochondrial serine protease with high homology to a bacterial survival factor, HtrA which protects bacterial cells from stress-induced toxicity due to misfolded proteins.

Methods: We directed the pan and dopaminergic neuronal expressions of wild-type α-syn to generate PD Drosophila model and co-expressions of wild-type α-syn and dOmi to generate a PD rescue fly's model. To investigate the ability of dOmi to protect against α-syn-induced neurotoxicity, we performed longevity, mobility, immunochemical, immunohistochemical, light, scanning electron and confocal microscopy studies to determine whether dOmi can rescue the α-syn-induced neurotoxicity in a Drosophila model of PD.

Results: Abnormal accumulation of α-syn, reduced lifespan, locomotor dysfunction, dopaminergic neuronal loss and rough eyes were resulted in 30-60-days-old α-syn transgenic Drosophila that indicates a toxic dominant mechanism of α-syn for the etiopathogenesis of PD. In contrast, both pattern of neuronal co-expressions of dOmi with α-syn showed that dOmi completely detoxified α-syn-induced neurotoxicity by degrading accumulated α-syn thereby preserved the normal numbers of dopaminergic neurons and normal eye ultra structure in aged flies. In addition, behavioral assays showed the increased lifespan along with strong positive locomotion, suggesting that this is an example of improved functional aging.

Conclusions: Our findings demonstrated a novel and important insights into the detoxification pathway of intraneuronal accumulated α-syn in a Drosophila model of PD, suggesting the neuroprotective role of dOmi that recapitulates the essential neuroprotective function of Omi in humans.

To cite this abstract, please use the following information:Rahman, M.M., Akhter, S., Islam, M.S., Kim, H.J., Hong, S.T.; Omi-mediated detoxification of α-synuclein-induced neurotoxicity in a drosophila model of Parkinson's disease [abstract]. Movement Disorders 2013;28 Suppl 1 :1180

http://www.mdsabstracts.com/abstract.asp?MeetingID=798&id=107223