Organization and Transport of Peroxisomes in Neurons

p0005 The potential role of peroxisomes in neurons is not well understood, except for the metabolism of very long-chain fatty acids. In human patients and in mice with peroxisome biogenesis disorders, neuronal migration is clearly affected. It is unclear whether this migration defect requires the function of peroxisomes in neuronal tissue or whether peroxisomes in nonneuronal tissues can provide this function. Experiments in mice show that the tissue-specific restoration of peroxisomes in the liver of mice deficient in peroxisome biogenesis does partially correct the neuronal migration deficits in the brain, but the restoration of peroxisomes in both tissues, rather than in only one, is more effective in restoring neuronal migration. It is also clear that a b-oxidation Au2 deficiency alone cannot cause neuronal migration defects, so other metabolic functions of peroxisomes may be involved. Mice lacking Pex11b, which is involved in peroxisome division, have only mild to no metabolic defects with respect to fatty acid b-oxidation and plasmalogen synthesis, but they still exhibit neuronal migration defects. These results emphasize that we still do not understand howorwhy peroxisomes affect neuronal migration and whether this is a direct or indirect effect. p0010 Peroxisomes are present in neural and astrocytic processes. The presence of peroxisomes in active growth cones with well-developed filopodia, varicosities, and neural terminal-like (presynaptic axon terminal) structures suggests their importance in the development and/or maintenance of neurites. Whereas many peroxisomes are found in long neurites with growth cones, only a small number exist in short neurites, leading to the suggestion that the short neurites are probably at rest since no growth cones have been observed. Therefore, it was postulated that the presence of peroxisomes in neurites helps their extending activity.