Neuronal ceroid lipofuscinosis: a common pathway?

Pediatr Res. 2007 Feb;61(2):146-52. doi: 10.1203/pdr.0b013e31802d8a4a.


The neuronal ceroid lipofuscinoses are pediatric neurodegenerative diseases with common clinical features. Of the nine clinical variants (CLN1-CLN9), six have been genetically identified. Most variants manifest cell death and dysregulated sphingolipid metabolism, suggesting the proteins defective in these disorders may interact along one pathway. NCL patient-derived cell lines exhibit cell growth and apoptotic defects that reverse following transfection with the wild-type gene. The membrane-bound proteins CLN3, CLN6, and CLN8 complement each other, as do CLN1 and CLN2 proteins, with respect to growth and apoptosis. The CLN2 protein also corrects growth and apoptosis in CLN3-, CLN6-, and CLN8-deficient cell lines. Neither CLN1-deficient nor CLN2-deficient growth defects are corrected by CLN3, CLN6, and CLN8 proteins. CLN2, CLN3, CLN6, and CLN8 proteins co-immunoprecipitate and co-localize to early and/or recycling endosomes and lipid rafts. Additionally, CLN2p and CLN1p co-immunoprecipitate. The work presented supports interactions between NCL proteins occurring at multiple points along one pathway.

MeSH terms

  • Animals
  • Apoptosis
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Humans
  • Immunoprecipitation
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Neuronal Ceroid-Lipofuscinoses / enzymology
  • Neuronal Ceroid-Lipofuscinoses / genetics
  • Neuronal Ceroid-Lipofuscinoses / metabolism*
  • Signal Transduction*
  • Time Factors
  • Transfection


  • Membrane Glycoproteins