Walkley S U
Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Brain Pathol. 1998 Jan;8(1):175-93. doi: 10.1111/j.1750-3639.1998.tb00144.x.
Lysosomal storage disorders are rare, inborn errors of metabolism characterized by intralysosomal accumulation of unmetabolized compounds. The brain is commonly a central focus of the disease process and children and animals affected by these disorders often exhibit progressively severe neurological abnormalities. Although most storage diseases result from loss of activity of a single enzyme responsible for a single catabolic step in a single organelle, the lysosome, the overall features of the resulting disease belies this simple beginning. These are enormously complex disorders with metabolic and functional consequences that go far beyond the lysosome and impact both soma-dendritic and axonal domains of neurons in highly neuron type-specific ways. Cellular pathological changes include growth of ectopic dendrites and new synaptic connections and formation of enlargements in axons far distant from the lysosomal defect. Other storage diseases exhibit neuron death, also occurring in a cell-selective manner. The functional links between known molecular genetic and enzyme defects and changes in neuronal integrity remain largely unknown. Future studies on the biology of lysosomal storage diseases affecting the brain can be anticipated to provide insights not only into these pathogenic mechanisms, but also into the role of lysosomes and related organelles in normal neuron function.
溶酶体贮积症是罕见的先天性代谢紊乱疾病，其特征是未代谢化合物在溶酶体内蓄积。大脑通常是疾病进程的核心关注点，受这些疾病影响的儿童和动物往往表现出逐渐严重的神经功能异常。尽管大多数贮积病是由于负责单个细胞器（即溶酶体）中单个分解代谢步骤的单一酶活性丧失所致，但由此产生的疾病的总体特征掩盖了这个简单的起因。这些是极其复杂的疾病，其代谢和功能后果远远超出溶酶体，并以高度神经元类型特异性的方式影响神经元的胞体-树突和轴突区域。细胞病理变化包括异位树突生长、新突触连接形成以及远离溶酶体缺陷的轴突膨大形成。其他贮积病也表现出神经元死亡，同样以细胞选择性方式发生。已知分子遗传和酶缺陷与神经元完整性变化之间的功能联系在很大程度上仍然未知。预计未来对影响大脑的溶酶体贮积病生物学的研究不仅能深入了解这些致病机制，还能深入了解溶酶体及相关细胞器在正常神经元功能中的作用。
