title: Dolichol and dolichyl phosphate in the neuronal ceroid-lipofuscinoses and other diseases.
abstract: Although, compared to age-matched control samples, nonphosphorylated dolichols are significantly increased in the cerebral cortex of children with the late infantile and juvenile types of neuronal ceroid-lipofuscinosis (NCL), dolichyl phosphates are increased to a much greater extent in infantile, late infantile, and juvenile forms of this disease group. Dolichyl phosphates in the cerebral cortex, expressed as a percentage of the combined nonphosphorylated and phosphorylated compounds, ranged from 59 to 85 (mean 71) in NCL, whereas in the non-NCL disease group the range is 18-36 (mean 25). This marked proportional increase in dolichyl phosphates is not unique to NCL but is also found in the brain of GM1-gangliosidosis and Tay-Sachs disease patients. In the liver from NCL patients, dolichyl phosphates are not a major proportion of the total dolichol compounds (1-9%). However, in the kidney and heart, dolichyl phosphates are again markedly increased, and this is associated with large storage of ceroid. Although to a lesser extent than in NCL, dolichols and dolichyl phosphates are significantly increased over levels in age-matched control samples in the temporal cortex in Alzheimer disease. Our interpretation of these results is that storage in secondary in secondary lysosomes in NCL and the gangliosidoses leads to a decrease in the catabolism of dolichyl phosphate compounds in the Golgi saccules or primary lysosomes.
authors.affiliation: Donner Laboratory of Experimental Neurochemistry, Montreal Neurological Institute and Hospital, Quebec, Canada.
authors.forename: L S
authors.initials: LS
authors.lastname: Wolfe
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: M
authors.initials: M
authors.lastname: Haltia
authors.forename: J
authors.initials: J
authors.lastname: Palo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000032:analysis*; D002675:Child, Preschool; D004288:Dolichol Phosphates / Q000032:analysis*; D004286:Dolichols / Q000032:analysis*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D009206:Myocardium / Q000032:analysis; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000032:analysis*; D013661:Tay-Sachs Disease / Q000378:metabolism
chemical_list: D004288:Dolichol Phosphates; D004286:Dolichols; D011106:Polyisoprenyl Phosphates