Neuroinflammatory and oxidative stress phenomena in MPS IIIA mouse model: the positive effect of long-term aspirin treatment.

Sanfilippo disease (MPS IIIA) is an autosomal recessive lysosomal storage disorder resulting from sulfamidase deficiency, which is characterized by severe neurological impairment. Various tissues of MPS IIIA mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, and are an excellent tool to both delineate disease pathogenesis and test potential therapies. The relationship between abnormal glycosaminoglycan storage and neurodysfunction remains ill defined.

Storage correction in cells of patients suffering from mucopolysaccharidoses types IIIA and VII after treatment with genistein and other isoflavones.

Mucopolysaccharidoses are autosomal and recessive lysosomal storage disorders caused by the deficiency of a lysosomal enzyme involved in glycosaminoglycan catabolism. The Sanfilippo type A disease (MPS III A) results from sulfamidase deficiency, which leads to accumulation of heparan sulfate, whereas Sly disease (MPS VII) results from beta-glucuronidase deficiency, leading to accumulation of heparan, dermatan, and chondroitin sulfates. These syndromes are characterized by severe central nervous system degeneration, resulting in progressive mental retardation, and fatality occurs in severely affected children.

Identification of new markers for neurodegeneration process in the mouse model of Sly disease as revealed by expression profiling of selected genes.

Sly disease (MPS VII) is an autosomal-recessive lysosomal storage disorder resulting from beta-glucuronidase deficiency, which is characterized by a severe neurological impairment. MPS VII mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, thus appearing to be an excellent tool to delineate disease pathogenesis. The relationship between abnormal glycosaminoglycan storage and neurodysfunction is not yet well understood, but inflammatory components can be involved, as in several neurological lysosomal disorders.

Glucocorticoids induce retinal toxicity through mechanisms mainly associated with paraptosis.

Purpose: Corticosteroids have recorded beneficial clinical effects and are widely used in medicine. In ophthalmology, besides their treatment benefits, side effects, including ocular toxicity have been observed especially when intraocular delivery is used. The mechanism of these toxic events remains, however, poorly understood.

Stable transmission of targeted gene modification using single-stranded oligonucleotides with flanking LNAs.

Targeted mutagenesis directed by oligonucleotides (ONs) is a promising method for manipulating the genome in higher eukaryotes. In this study, we have compared gene editing by different ONs on two new target sequences, the eBFP and the rd1 mutant photoreceptor betaPDE cDNAs, which were integrated as single copy transgenes at the same genomic site in 293T cells. Interestingly, antisense ONs were superior to sense ONs for one target only, showing that target sequence can by itself impart strand-bias in gene editing.