title: Functional biology of the neuronal ceroid lipofuscinoses (NCL) proteins.
abstract: Neuronal ceroid lipofucinoses (NCLs) are a group of severe neurodegenerative disorders characterized by accumulation of autofluorescent ceroid lipopigment in patients' cells. The different forms of NCL share many similar pathological features but result from mutations in different genes. The genes affected in NCLs encode both soluble and transmembrane proteins and are localized to ER or to the endosomes/lysosomes. Due to selective vulnerability of the central nervous system in the NCL disorders, the corresponding proteins are proposed to have important, tissue specific roles in the brain. The pathological similarities of the different NCLs have led not only to the grouping of these disorders but also to suggestion that the NCL proteins function in the same biological pathway. Despite extensive research, including the development of several model organisms for NCLs and establishment of high-throughput techniques, the precise biological function of many of the NCL proteins has remained elusive. The aim of this review is to summarize the current knowledge of the functions, or proposed functions, of the different NCL proteins.
authors.affiliation: National Public Health Institute, Department of Molecular Medicine, Biomedicum Helsinki, Helsinki, Finland. aija.kyttala@ktl.fi
authors.forename: Aija
authors.initials: A
authors.lastname: Kyttälä
authors.forename: Ulla
authors.initials: U
authors.lastname: Lahtinen
authors.forename: Thomas
authors.initials: T
authors.lastname: Braulke
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Hofmann
mesh_terms: D000626:Aminopeptidases; D000818:Animals; D002403:Cathepsins / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D057057:Serine Proteases; D013869:Thiolester Hydrolases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C105199:CLN3 protein, human; C113332:CLN5 protein, human; C447500:CLN6 protein, human; C121767:CLN8 protein, human; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human; D002403:Cathepsins; D010450:Endopeptidases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases