Adrenoleukodystrophy; Alzheimer Disease; Peroxisomal Disorders; Peroxisomes; Plasmalogens
My main research focus is to understand the importance of different peroxisomal metabolic pathways for the proper function of the brain. The research is designed to elucidate molecular mechanisms underlying the different phenotypes of X-linked adrenoleukodystrophy and to develop novel therapeutic approaches. The ether phospholipid biosynthesis is disturbed in a group of inherited peroxisomal disorders but increasing evidence emerges suggesting a role of ether phospholipids in the pathogenesis of late onset neurodegenerative diseases such as Alzheimer’s disease. Thus, the characterization of molecular consequence of ether phospholipid deficiency for the nervous system is another focus of our laboratory.
Techniques, methods & infrastructure
Mouse models for X-linked adrenoleukodystrophy, ether phospholipid deficiency or Alzheimer’s disease are used for in vivo analysis and primary cells from human patients (e.g. monocytes, lymphoblast or fibroblasts) for in vitro analysis of the role of peroxisomes in proper cellular functioning. A broad spectrum of biochemical, cell biological, and imaging techniques are used.
- Dorninger, F. et al., 2019. Disturbed neurotransmitter homeostasis in ether lipid deficiency. Human Molecular Genetics, 28(12), pp.2046–2061. Available at: http://dx.doi.org/10.1093/hmg/ddz040.
- Dorninger, F. et al., 2018. Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer’s Disease Mimic Accelerated Aging. Journal of Alzheimer’s Disease, 62(2), pp.841–854. Available at: http://dx.doi.org/10.3233/JAD-171036.
- Weinhofer, I. et al., 2018. Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain, 141(8), pp.2329–2342. Available at: http://dx.doi.org/10.1093/brain/awy127.
- Facciotti, F. et al., 2012. Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nature Immunology, 13(5), pp.474–480. Available at: http://dx.doi.org/10.1038/ni.2245.
- Kou, J. et al., 2011. Peroxisomal alterations in Alzheimer’s disease. Acta Neuropathologica, 122(3), pp.271–283. Available at: http://dx.doi.org/10.1007/s00401-011-0836-9.