We show that amphiphile-mediated depalmitoylation (AMD) can effectively cleave S-palmitoyl groups from the native GTPase HRas and successfully depalmitoylate mislocalized proteins in an infantile neuronal ceroid lipofuscinosis (INCL) disease model.
Infantile neuronal ceroid lipofuscinosis (INCL; NCL1, Haltia-Santavuori disease) is caused by mutations in the CLN1/PPT gene which are associated with an early onset INCL phenotype.
Although the clinical and pathological features of the GFAP(-/-)Vimentin(-/-)PPT1(-/-) mice are similar to INCL, the disease appears earlier and progresses more rapidly.
We report here that, in cultured INCL fibroblasts and in the brain tissues of Ppt1-KO mice, the NAD(+)/NADH ratio, the levels of phosphorylated-AMPK (p-AMPK), peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) and Silent Information Regulator T1 (SIRT1) are markedly down-regulated.
Most importantly, resveratrol (RSV), an antioxidant polyphenol, elevated the NAD(+)/NADH ratio, levels of ATP, p-AMPK, PGC-1α and SIRT1 while decreasing the level of p-S6K1 in both INCL fibroblasts and in Ppt1-KO mice, which showed a modest increase in lifespan.
Although the clinical and pathological features of the GFAP(-/-)Vimentin(-/-)PPT1(-/-) mice are similar to INCL, the disease appears earlier and progresses more rapidly.
We also demonstrate that transfection of cultured INCL cells with a green fluorescent protein-GAP-43 cDNA construct shows abnormal localization of this protein in the ER.
Here we report that in the human INCL brain ER stress-induced activation of unfolded protein response (UPR) mediates caspase-4 and caspase-3 activation and apoptosis.
Here we report that in the human INCL brain ER stress-induced activation of unfolded protein response (UPR) mediates caspase-4 and caspase-3 activation and apoptosis.
In the present study, new PCR-OLA methods were developed for the detection of the major mutations causing infantile neuronal ceroid lipofuscinosis (INCLFin), congenital nephrotic syndrome of Finnish type (NPHS1 FinMajor and FinMinor) and medium chain acyl-CoA dehydrogenase deficiency (MCAD A985G).
Assignment of sterol carrier protein X/sterol carrier protein 2 to 1p32 and its exclusion as the causative gene for infantile neuronal ceroid lipofuscinosis.
Here we demonstrate a linkage disequilibrium of CLN1 chromosomes using the two closest markers, DIS62 and L-MYC at the short arm of chromosome 1 (P less than 0.0025).
The palmitoyl protein thioesterase-2 (PPT2) gene encodes a lysosomal thioesterase homologous to PPT1, which is the enzyme defective in the human disorder called infantile neuronal ceroid lipofuscinosis.
PPT2 is located in the human major histocompatibility class III locus on chromosome 6p21.3, a position that rules outPPT2 as the causative gene in any of the NCLs at defined chromosomal loci.
Infantile neuronal ceroid lipofuscinosis (INCL; NCL1, Haltia-Santavuori disease) is caused by mutations in the CLN1/PPT gene which are associated with an early onset INCL phenotype.
Infantile neuronal ceroid lipofuscinosis (INCL; NCL1, Haltia-Santavuori disease) is caused by mutations in the CLN1/PPT gene which are associated with an early onset INCL phenotype.
Mutations in the palmitoyl-protein thioesterase (PPT) gene cause infantile neuronal ceroid lipofuscinosis (INCL), the clinical manifestations of which include the early loss of vision followed by deterioration of brain functions.
In a pregnancy at risk for INCL, chorionic villi (CV) were studied using a novel fluorometric PPT enzyme assay in combination with mutation-analysis of the CLN1 gene.
In a pregnancy at risk for INCL, chorionic villi (CV) were studied using a novel fluorometric PPT enzyme assay in combination with mutation-analysis of the CLN1 gene.
Mutations in the palmitoyl-protein thioesterase (PPT) gene cause infantile neuronal ceroid lipofuscinosis (INCL), the clinical manifestations of which include the early loss of vision followed by deterioration of brain functions.
We pursued the identification of the gene defective in INCL, enriched in the Finnish population by a positional cloning approach and identified mutations in the palmitoyl-protein thioesterase (PPT) gene in INCL patients.
We pursued the identification of the gene defective in INCL, enriched in the Finnish population by a positional cloning approach and identified mutations in the palmitoyl-protein thioesterase (PPT) gene in INCL patients.