title: NCL disease mechanisms.
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.
authors.affiliation: Department of Wine, Food and Molecular Biosciences, Faculty of Agricultural and Life Sciences, Lincoln University, PO Box 85084, Lincoln 7647, Christchurch, New Zealand. Electronic address: david.palmer@lincoln.ac.nz.
authors.forename: David N
authors.initials: DN
authors.lastname: Palmer
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Barry
authors.forename: Jaana
authors.initials: J
authors.lastname: Tyynelä
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D008247:Lysosomes / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D010641:Phenotype
chemical_list: D008565:Membrane Proteins
keywords: Biochemical abnormalities; Glial activation; Pathogenesis; Selective neuron loss; Storage material accumulation; Synaptic pathology