Abnormally accumulated GM2 ganglioside contributes to skeletal deformity in Tay-Sachs mice.

Tay-Sachs Disease is a rare lysosomal storage disorder caused by mutations in the HEXA gene, responsible for the degradation of ganglioside GM2. In addition to progressive neurodegeneration, Tay-Sachs patients display bone anomalies, including kyphosis. Tay-Sachs disease mouse model (Hexa-/-Neu3-/-) shows both neuropathological and clinical abnormalities of the infantile-onset disease phenotype.

Analysis of Brain Lipids in the Early-Onset Tay-Sachs Disease Mouse Model With the Combined Deficiency of β-Hexosaminidase A and Neuraminidase 3.

Tay-Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the gene coding β-hexosaminidase A. gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of β-hexosaminidase A and neuraminidase 3 () that mimics both the neuropathological and clinical abnormalities of early-onset Tay-Sachs disease.

Sialidase neu4 deficiency is associated with neuroinflammation in mice.

Sialidases catalyze the removal of sialic acid residues from glycoproteins, oligosaccharides, and sialylated glycolipids. Sialidase Neu4 is in the lysosome and has broad substrate specificity. Previously generated Neu4-/- mice were viable, fertile and lacked gross morphological abnormalities, but displayed a marked vacuolization and lysosomal storage in lung and spleen cells.

GM2 ganglioside accumulation causes neuroinflammation and behavioral alterations in a mouse model of early onset Tay-Sachs disease.

Background: Tay-Sachs disease (TSD), a type of GM2-gangliosidosis, is a progressive neurodegenerative lysosomal storage disorder caused by mutations in the α subunit of the lysosomal β-hexosaminidase enzyme. This disease is characterized by excessive accumulation of GM2 ganglioside, predominantly in the central nervous system. Although Tay-Sachs patients appear normal at birth, the progressive accumulation of undegraded GM2 gangliosides in neurons leads to death.

The Second Case of Saposin A Deficiency and Altered Autophagy.

Krabbe disease is a lysosomal storage disease caused by galactosylceramidase deficiency, resulting in neurodegeneration with a rapid clinical downhill course within the first months of life in the classic infantile form. This process may be triggered by the accumulation of galactosylceramide (GalCer) in nervous tissues. Both the enzyme galactosylceramidase and its in vivo activator molecule, saposin A, are essential during GalCer degradation.

Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.

Tay-Sachs disease is a severe lysosomal storage disorder caused by mutations in Hexa, the gene that encodes for the α subunit of lysosomal β-hexosaminidase A (HEXA), which converts GM2 to GM3 ganglioside. Unexpectedly, Hexa mice have a normal lifespan and show no obvious neurological impairment until at least one year of age. These mice catabolize stored GM2 ganglioside using sialidase(s) to remove sialic acid and form the glycolipid GA2, which is further processed by β-hexosaminidase B.

Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides.

Lysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. CTSA present in the lysosomal multienzyme complex to facilitate the correct lysosomal routing, stability and activation of with beta-galactosidase and alpha-neuraminidase. Beside CTSA has role in inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of 1 or 2 amino acid(s) from C-terminal ends.

Effects of cell-mediated osteoprotegerin gene transfer and mesenchymal stem cell applications on orthodontically induced root resorption of rat teeth.

Aim: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR).

Materials And Methods: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]. About 100g of orthodontic force was applied to upper first molar teeth of rats for 14 days.