Notably, we found that the HR domain in ACTL6A was essential for regulating GCLC expression
In another embodiment of the invention, lysosomal storage diseases (LSDs) are treated with one of the following targeted drugs or compounds based on drugs and compounds that cause reduction of lysosomal stored materials like glucocerebroside, sphingomyelin, ceramide, G Ml -ganglioside, G M2 -ganglioside, globoside, galactosylceramide, dermatan sulfate, heparan sulfate, keratan sulfate, sulfatides, mucopolysaccharides, sialyloligosaccharides, glycoproteins, sialyloligosaccharides, glycolipids, globotriaosylceramide, O-linked glycopeptides, glycogen, free sialic acid, fucoglyco lipids, fucosyloligosaccharides, mannosyloligosaccharides, aspartylglucosamine, cholesteryl esters, triglycerides, and ceroid lipofuscin pigments in lysosomal storage diseases, like Gaucher disease (stored glucocerebroside) using targeted enzyme replacement therapy with beta-glucocerebrosidase (e.g., imiglucerase (Cerezyme marketed by Genzyme) or velalglucerase (in development by Shire), gene- activated beta-glucocerebrosidase, or with substrate inhibition of glucosylceramide synthase with imino sugars (e.g., miglustat (Zavesca marketed by Actelion) = N-butyl- deoxynojirimycin (NB-DNJ), N-butyl-galactosyl-deoxynojirimycin (NB-DGJ), N-(5- adamantane-1-yl-methoxypentyl)- deoxynojirimycin (AMP-DNJ), N-(5-adamantane-l- yl-methhoxy-pentyl)deoxynojirimycin (AMP-DNM), or with Glucosylceramide analogs (e.g., Genz 112638: d-threo-ethylendioxyphenyl-2-palmitoylamino-3- pyrrilidino-propanol), or with chaperone therapy (e.g., isofagomine tartrate, AT2101, (to be marketed as Plicera by Amicus Therapeutics, chemical name: (3R, 4R, 5R)- 3,4-Dihydroxy-5-hydroxymethyl-piperidine)
No mathematical model can track all of the variables that might affect a complex biochemical system such as glutathione metabolism
It would be important to measure baseline and provoked 24hour urine mercury levels in patients with hypertension with a history or clinical evidence of possible mercury exposure
Nguyen, L.-T., Schmidt, H
