CNS/PNS pathology	Pathophysiological lessons
Axonal degeneration of sciatic nerve and spinal cord long tracts Myelin thickening in sciatic nerve Slow nerve conduction velocity with normal amplitude Axonal damage reversed with antioxidant supplementation No CNS immune system invasion No CNS demyelination	AMN-like late onset, progressive neurodegenerative phenotype with peripheral nerve axonal damage and hypermyelination. Axonal damage precedes myelin abnormalities Oxidative stress as a driving force for axonal damage Abcd2 overexpression reverts PNS neurodegeneration No CNS involvement No increase in neuroglial apoptosis
Reduction in myelin component proteolipid protein 1a Reduction in myelinated axons 30% reduction of oligodendrocyte progenitor cells Oligodendrocyte-produced myelin basic protein was unaltered	Model shows increase in C26:0, competitive disadvantage, and reduction in oligodendrocyte progenitor cells, reversible with human ABCD1 rescue Competitive disadvantage Increase in brain apoptosis, however not of oligodendrocytes Modest increase in VLCFA, life span reduction and decrease in oligodendrocytes
Axonal damage of GABAergic motor neurons Similar axonal damage was seen by knockdown of mitochondrial complex I subunit	Model shows increase C26:0, axonal damage, and susceptibility to ROS Axonal damage similar to mitochondrial dysfunction, ameliorated by antioxidants Accumulation of lipid droplets Decrease in life span when exposed to complex I, II, and IV inhibitors Axonal damage was not rescued by the overexpression of WT Pmp-4 No similar redox imbalance with peroxisomal thiolase deficiency
Vacuoles and disrupted pigment cells between ommatidia Lipid droplet formation	Model shows neuronal (retinal) degeneration No information regarding VLCFA accumulation, flight quality, or life span Neuron-specific and not glia-specific knockdown of dABCD caused retinal degeneration
Similar to Abcd1 deficiency	Similar to Abcd1 deficiency
Loss of photoreceptors Vacuoles and disrupted pigment cells between ommatidia Suppression by medium chain rich food	Neuronal (retinal) degeneration seen also with disruption of the “upstream” long-chain fatty acid activation pathway Model shows C26:1 elevation, reduced life span and decreased flight ability Reversed VLCFA elevation upon supplementation with glyceryl trioleate oil Similar retinal neurodegeneration observed with knocking down dABCD and elongase (dELOVL), both independently responsible for activated fatty acid products No exacerbation of symptoms with VLCFA-rich food Medium-chain rich food did not revert reduced life span or decreased flight quality