神经元蜡样脂褐质沉淀：旧病的新视野

Title:Neuronal Ceroid Lipofuscinosis: The Increasing Spectrum of an Old Disease

Volume: 14 Issue: 8

Author(s): A. Simonati, F. Pezzini, F. Moro and F.M. Santorelli

Affiliation:

关键词: 神经元蜡样脂褐质传染病，神经元蜡样脂褐质基因，神经元蜡样脂褐质发病机理，神经元蜡样脂褐质病理学，神经元蜡样脂褐质表型，神经元蜡样脂褐质治疗。

摘要: Neuronal Ceroid Lipofuscinoses (NCL) are genetically heterogeneous heritable neurodegenerative disorders with worldwide distribution. They are considered as childhood diseases; however rare adult onset forms are known. NCL have a progressive course, affecting visual, motor and cognitive functions, and are associated with myoclonic epilepsy; behavioural problems can be observed at the onset. The outcome is invariably fatal, mostly during the second or third decade. The denomination is based on pathological criteria, i.e. the presence of intralysosomal storage of autofluorescent lipopigment of glycoprotein origin with characteristic ultrastructural features. The NCL are autosomal recessive diseases (but a rare autosomal dominant form of adult onset). Thirteen NCL associated genes have been identified so far, which allow a definite diagnosis to be reached and provide genetic counselling to the families. Still unidentified NCL genes are foreseen. Allelic heterogeneity is observed in some mutated genes; likewise phenotypic heterogeneity is seen in several NCL. The gene products are either soluble proteins (such as lysosomal enzymes) or membrane proteins related to lysosomes, endoplasmic reticulum, synaptic vesicles. Little is known about pathogenetic mechanisms, leading to storage formation and cell death. Current research is focusing on intracellular trafficking, neurotransmission and storage removal. No cure is available for any form. Innovative treatments led to some results in mouse models related to lysosome hydrolase defects. Evidences that autophagy, oxidative stress, excitotoxicity play roles in NCL cell pathology raise the possibility that selected steps of these processes might become target of treatments, and therefore modify the disease course.

Cite this article as:

Simonati A., Pezzini F., Moro F. and Santorelli F.M., Neuronal Ceroid Lipofuscinosis: The Increasing Spectrum of an Old Disease, Current Molecular Medicine 2014; 14 (8) . https://dx.doi.org/10.2174/1566524014666141010154913