De Munter Stephanie, Verheijden Simon, Régal Luc, Baes Myriam
Department of Pharmaceutical and Pharmacological Sciences, Cell Metabolism, KU Leuven-University of Leuven, B-3000, Leuven, Belgium.
Department of Clinical and Experimental Medicine, TARGID, KU Leuven-University of Leuven, B-3000, Leuven, Belgium.
Brain Pathol. 2015 Nov;25(6):663-78. doi: 10.1111/bpa.12290. Epub 2015 Aug 19.
Peroxisomes are organelles with diverse metabolic tasks including essential roles in lipid metabolism. They are of utmost importance for the normal functioning of the nervous system as most peroxisomal disorders are accompanied with neurological symptoms. Remarkably, the cerebellum exquisitely depends on intact peroxisomal function both during development and adulthood. In this review, we cover all aspects of cerebellar pathology that were reported in peroxisome biogenesis disorders and in diseases caused by dysfunction of the peroxisomal α-oxidation, β-oxidation or ether lipid synthesis pathways. We also discuss the phenotypes of mouse models in which cerebellar pathologies were recapitulated and search for connections with the metabolic abnormalities. It becomes increasingly clear that besides the most severe forms of peroxisome dysfunction that are associated with developmental cerebellar defects, milder impairments can give rise to ataxia later in life.
过氧化物酶体是具有多种代谢任务的细胞器，包括在脂质代谢中发挥重要作用。它们对神经系统的正常功能至关重要，因为大多数过氧化物酶体疾病都伴有神经症状。值得注意的是，小脑在发育和成年期都极其依赖完整的过氧化物酶体功能。在这篇综述中，我们涵盖了过氧化物酶体生物发生障碍以及由过氧化物酶体α-氧化、β-氧化或醚脂合成途径功能障碍引起的疾病中所报道的小脑病理学的各个方面。我们还讨论了重现小脑病理学的小鼠模型的表型，并寻找与代谢异常的联系。越来越清楚的是，除了与发育性小脑缺陷相关的最严重形式的过氧化物酶体功能障碍外，较轻的损伤也可能在以后的生活中导致共济失调。
