NCL disease mechanisms

David N. Palmer*, Lucy A. Barry, Jaana Tyynela, Jonathan D. Cooper

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

92 Citations (Scopus)

Abstract

Despite the identification of a large number of disease-causing genes in recent years, it is still unclear what disease mechanisms operate in the neuronal ceroid lipofuscinoses (NCLs, Batten disease). As a group they are defined by the specific accumulation of protein, either subunit c of mitochondrial ATP synthase or SAPs A and D in lysosome-derived organelles, and regionally specific neurodegeneration. Evidence from biochemical and cell biology studies indicates related lesions in intracellular vesicle trafficking and lysosomal function. There is also extensive immunohistological evidence of a causative role of disease associated neuroinflammation. However the nature of these lesions is not clear nor is it clear why they lead to the defining pathology. Several different theories have proposed a range of potential mechanisms, but it remains to be determined which are central to pathogenesis, and whether there is a mechanism consistent across the group, or if it differs between disease forms. This review summarises the evidence that is currently available and the progress that has been made in understanding these profoundly disabling disorders. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

Original languageEnglish
Article numberN/A
Pages (from-to)1882-1893
Number of pages12
JournalBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume1832
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Pathogenesis
  • Selective neuron loss
  • Glial activation
  • Synaptic pathology
  • Storage material accumulation
  • Biochemical abnormalities
  • NEURONAL-CEROID-LIPOFUSCINOSIS
  • PALMITOYL-PROTEIN THIOESTERASE
  • MITOCHONDRIAL ATP SYNTHASE
  • JUVENILE BATTEN-DISEASE
  • TRIPEPTIDYL-PEPTIDASE-I
  • CATHEPSIN-D DEFICIENCY
  • SOUTH HAMPSHIRE SHEEP
  • MANNOSE 6-PHOSPHATE GLYCOPROTEOME
  • LYSOSOMAL STORAGE DISEASE
  • CENTRAL-NERVOUS-SYSTEM

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