Neuronal Ceroid Lipofuscinosis: The increasing spectrum of an old disease

A. Simonati, F. Pezzini, F. Moro, F. M. Santorelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1043-1051
Number of pages9
JournalCurrent Molecular Medicine
Volume14
Issue number8
Publication statusPublished - Mar 1 2014

Keywords

  • NCL epidemiology
  • NCL genes
  • NCL pathogenesis
  • NCL pathology
  • NCL phenotypes
  • NCL treatments

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

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    Simonati, A., Pezzini, F., Moro, F., & Santorelli, F. M. (2014). Neuronal Ceroid Lipofuscinosis: The increasing spectrum of an old disease. Current Molecular Medicine, 14(8), 1043-1051.