Miro, a Rho GTPase genetically interacts with Alzheimer's disease-associated genes ( Tau, Aβ ₄₂ and Appl) in Drosophila melanogaster

Miro (mitochondrial Rho GTPases), a mitochondrial outer membrane protein, facilitates mitochondrial axonal transport along the microtubules to facilitate neuronal function. It plays an important role in regulating mitochondrial dynamics (fusion and fission) and cellular energy generation. Thus, Miro might be associated with the key pathologies of several neurodegenerative diseases (NDs) including Alzheimer's disease (AD). In the present manuscript, we have demonstrated the possible genetic interaction between Miro and AD-related genes such as Tau, Aβ ₄₂ and Appl in Drosophila melanogaster Ectopic expression of Tau, Aβ ₄₂ and Appl induced a rough eye phenotype, defects in phototaxis and climbing activity, and shortened lifespan in the flies. In our study, we have observed that overexpression of Miro improves the rough eye phenotype, behavioral activities (climbing and phototaxis) and ATP level in AD model flies. Further, the improvement examined in AD-related phenotypes was correlated with decreased oxidative stress, cell death and neurodegeneration in Miro overexpressing AD model flies. Thus, the obtained results suggested that Miro genetically interacts with AD-related genes in Drosophila and has the potential to be used as a therapeutic target for the design of therapeutic strategies for NDs.

Keywords: Alzheimer's disease; Appl; Aβ42; Miro; Mitochondria; Tau.