Neuronal ceroid lipofuscinoses and possible pathogenic mechanism.
The neuronal ceroid lipofuscinoses (NCLs) consist of eight autosomal recessively inherited storage disorders characterized by lysosomal inclusions of autofluorescent lipofuscins and rapid neurodegenerative progression. The NCLs include eight forms that result from genetic deficiency on genes CLN(1) to CLN(8), respectively: four classic forms with clinical onset at varying ages-infantile (INCL), late-infantile (LINCL), juvenile (JNCL), and adult (ANCL)-and four variants of late-infantile onset-the Finnish variant LINCL (fLINCL), Portuguese variant LINCL (pLINCL), Turkish variant LINCL (tLINCL), and progressive epilepsy with mental retardation (EPMR). The genes CLN(1) and CLN(2) have been characterized to encode lysosomal hydrolytic enzymes, but CLN(3), CLN(5), and CLN(8) encode transmembranous proteins with unknown function. Although clinical and pathological abnormalities have been recognized to be similar in all eight forms, the molecular mechanism explaining NCL pathogenesis remains unclear. In this review, the molecular basis for NCLs and a possible pathogenic mechanism are discussed.
Zhong
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New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA. omrddzhong@aol.com
D000328:Adult; D000626:Aminopeptidases; D017209:Apoptosis; D002648:Child; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D008247:Lysosomes / Q000201:enzymology; D008562:Membrane Glycoproteins; D008967:Molecular Biology; D018832:Molecular Chaperones; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1
C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011506:Proteins; D000091346:Tripeptidyl-Peptidase 1; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases