Herein, we discuss the molecular and antigenic properties of AFP which make it a disordered protein, and its ability to induce autoantibody production to AFP cryptic epitopes in both HHC and BD patients.
Herein, we discuss the molecular and antigenic properties of AFP which make it a disordered protein, and its ability to induce autoantibody production to AFP cryptic epitopes in both HHC and BD patients.
Although the molecular targets of aberrant caspase 1 activity in the context of CLN3 mutation remain to be identified, our studies suggest that caspase 1 may represent a potential therapeutic target to mitigate some attributes of CLN3 disease.
Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively.
The strongest signal was observed at 16p12.1 (25 cM, 33 Mb; heterogeneity logarithm of odds = 5.3), ∼3 Mb upstream of the ceroid lipofuscinosis 3 (<i>CLN3</i>) gene associated with juvenile neuronal ceroid lipofuscinosis (JNCL), which functions in retromer trafficking and has been reported to alter intracellular processing of the amyloid precursor protein.
Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively.
Molecular mechanisms of the juvenile form of Batten disease: important role of MAPK signaling pathways (ERK1/ERK2, JNK and p38) in pathogenesis of the malady.
Treatment with neuronal lysates and ceramide, a lipid intermediate elevated in the JNCL brain, led to inflammasome activation and IL-1β release in CLN3(Δex7/8) microglia but not WT cells, as well as increased expression of additional pro-inflammatory mediators.
We observed an increased expression of PDH and a decreased expression of ACL, PEPCK, and acetyl-GD3 in BD lymphoblast cells compared to normal cells, possibly resulting in the high ROS levels, mitochondrial membrane depolarization, and apoptosis typically found in BD.
The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP-2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease.
The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP-2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease.
The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP-2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease.
This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease.
In this review, we discuss how studies in yeast models have already resulted in significant insights into the understanding of neurodegenerative disorders that include prion disease, Parkinson's disease, polyglutamine expansion disorders, Friedreich's ataxia, and Batten disease.
In the last five years, specific mutations have been defined in Lafora disease (gene for laforin or dual specificity phosphatase in 6q24), Unverricht-Lundborg disease (cystatin B in 21q22.3), Jansky-Bielschowsky ceroid lipofuscinoses (CLN2 gene for tripeptidyl peptidase 1 in 11q15), Finnish variant of late infantile ceroid lipofuscinoses (CLN5 gene in 13q21-32 encodes 407 amino acids with two transmembrane helices of unknown function), juvenile ceroid lipofuscinoses or Batten disease (CLN3 gene in 16p encodes 438 amino acid protein of unknown function), a subtype of Batten disease and infantile ceroid lipofuscinoses of the Haltia-Santavuori type (both are caused by mutations in palmitoyl-protein thiosterase gene at 1p32), dentadorubropallidoluysian atrophy (CAG repeats in a gene in 12p13.31) and the mitochondrial syndrome MERRF (tRNA Lys mutation in mitochondrial DNA).
In the last five years, specific mutations have been defined in Lafora disease (gene for laforin or dual specificity phosphatase in 6q24), Unverricht-Lundborg disease (cystatin B in 21q22.3), Jansky-Bielschowsky ceroid lipofuscinoses (CLN2 gene for tripeptidyl peptidase 1 in 11q15), Finnish variant of late infantile ceroid lipofuscinoses (CLN5 gene in 13q21-32 encodes 407 amino acids with two transmembrane helices of unknown function), juvenile ceroid lipofuscinoses or Batten disease (CLN3 gene in 16p encodes 438 amino acid protein of unknown function), a subtype of Batten disease and infantile ceroid lipofuscinoses of the Haltia-Santavuori type (both are caused by mutations in palmitoyl-protein thiosterase gene at 1p32), dentadorubropallidoluysian atrophy (CAG repeats in a gene in 12p13.31) and the mitochondrial syndrome MERRF (tRNA Lys mutation in mitochondrial DNA).
The gene responsible for the human juvenile form of neuronal ceroid lipofuscinosis (CLN3), maps close to TSC2 and PKD1 in humans, and is also syntenic in the dog.
Furthermore, the severity of Batten disease in humans and the degree of ANP resistance in yeast are related when the equivalent amino acid replacements in Cln3p and Btn1p are compared.
Analysis of disease haplotypes for four microsatellite markers in this interval, D16S288, D16S299, D16S298, and SPN, has shown significant allelic association between one allele at each of these loci and CLN3.