title: The molecular genetic basis of the neuronal ceroid lipofuscinoses.
abstract: The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the presence of autofluorescent lipopigment in neurons and other cell types. The childhood onset types display autosomal recessive inheritance. Naturally occurring animal NCLs have been described in many species including mouse, sheep and dog. In the last decade major advances have occurred in the molecular genetic analysis of the NCLs. Six disease gene loci have been mapped, and five disease genes have been isolated. Two of these encode lysosomal enzymes: CLN1 encodes palmitoyl-protein thioesterase (PPT), and CLN2 encodes tripeptidyl peptidase 1 (TPP1). The remaining three, CLN3, CLN5 and CLN8 encode putative membrane proteins of unknown function. The murine orthologue of CLN8 causes motor neuron degeneration (mnd), a mouse model of NCL. These advances have revolutionized diagnosis and classification, but a unified theory of pathogenesis and effective treatment remain elusive.
authors.affiliation: Department of Paediatrics, Royal Free & University College Medical School, University College London, The Rayne Institute, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
mesh_terms: D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D005192:Family Health; D008040:Genetic Linkage; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D057057:Serine Proteases; D013869:Thiolester Hydrolases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C105199:CLN3 protein, human; C113332:CLN5 protein, human; C121767:CLN8 protein, human; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; C000717268:Tpp1 protein, mouse; D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human