Parkinson Hastalığının Drosophila Modelinde Nutraceutical Dehydrozingerone ve C2- simetrik Dimerinin Nöroprotektif Etkileri

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamin-ergic neurons responsible for unintended or uncontrollable movements. Mutations in leu-cine-rich repeat kinase 2 locus, contributes to genetic forms of PD. The fruit fly Drosophila mela-nogaster carrying this mutation (LRRK2-Dm), is an in vivo model of PD that develops motor impairment and stands for an eligible non mammalian paradigm to test novel therapeutic ap-proaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger. Pre-sents anti-inflammatory, antioxidant and neuroprotective properties making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1mM, for 14 and 21 days, in the LRRK2-Dm, with the aim to assess changes for rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-Bars). The shorter treat-ment with both molecules revealed efficacy at the higher dose improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-Bars failure was observed with the DHZ-DIM. Our data indicates that the DHZ-DIM exerts a more potent neuroprotective effect respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

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