*4.4. Insect*

An X-ALD fly model has been generated in *Drosophila melanogaster* using RNA interfering of *dABCD*, the ortholog of *ABCD1*. These flies survive to adulthood but exhibit a specific brain neurodegenerative phenotype with retinal defects including holes and loss of pigment cells associated with death of neurons and glia [116]. Interestingly, cellular targeted disruption of *dABCD* in neurons, but not in glia, triggers the retinal defects. The phenotype is indistinguishable from the one observed in *bgm* (bubblegum) and *dbb* (double-bubble) deficient flies [117]. Both *bgm* and *dbb* genes code for long/very-long-chain acyl-CoA synthetases. The shared neurodegenerative features in *dABCD* and *bgm*/*dbb* deficient flies show that the lipid metabolic pathway is a key component of the X-ALD-like neurodegenerative disease in *Drosophila*. More specifically, experiments achieved with *bgm* and *dbb* deficient flies indicate that the loss of metabolites is the cause of neurodegenerative disease rather than accumulation of substrates (V/LCFAs), as was commonly thought.
