To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB ...

Sandhoff Disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the Hexb gene for the β-subunit of β-hexosaminidase A, resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2 primarily in the CNS. Myelin-enriched glycolipids, cerebrosides and sulfatides, are also decrea...

Tay-Sachs disease is a prototypic neurodegenerative disease. Lysosomal storage of GM2 ganglioside in Tay-Sachs and the related disorder, Sandhoff disease, is caused by deficiency of beta-hexosaminidase A, a heterodimeric protein. Tay-Sachs-related diseases (GM2 gangliosidoses) are incurable, but gene therapy has the potential for widespread correction of the underlying lysosomal defect by means...

2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide derivatives were synthesized and their structures were confirmed by 1H NMR, IR, and elemental analysis. Cytotoxicity of the compounds towards HEK-293 and GMK cells was evaluated. Moreover, the antiviral and virucidal activities of these compounds against human adenovirus type 5 and ECHO-9 virus were assessed. Some of the newly synthesized de...

Our objective was to analyze the effect of gender on the relationship between stroke rates corresponding to critical speed (SRCS) and maximal speed of 30 min (SRS30) in young swimmers. Twenty two males (GM1) (Age = 15.4 ± 2.1 yr., Body mass = 63.7 ± 12.9 kg, Stature = 1.73 ± 0.09 m) and fourteen female (GF) swimmers (Age = 15.1 ± 1.6 yr., Body mass = 58.3 ± 8.8 kg, Stature = 1.65 ± 0.06 m) were...

While searching for novel nonsteroidal inhibitors of human and rat prostatic 5alpha-reductases, we found a new series of indoline and aniline derivatives that showed potent inhibitory activities for both enzymes. Among them, 3-chloro-4-¿[1-(4-phenoxybenzyl)indolin-5-yl]oxylbenzoic acid (2e, YM-36117) showed a more potent inhibitory activity for the human enzyme than ONO-3805 with an IC50 value ...

The molecular mechanism underlying Akt activation in zinc-induced cardioprotection 1 SungRyul Lee, Guillaume Chanoit, Rachel McIntosh, David A. Zvara, Zhelong Xu 2 Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 3 27599 4 5 Running head: Zinc and Akt activation 6 7 Correspondence to: 8 Zhelong Xu, MD, PhD 9 Department of Anesthesiology 10 CB# 7010 11 U...