Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human N-acetyl-beta-D-glucosaminidase, N-acetyl-alpha-D-glucosaminidase, endo-beta-N-acetylglucosaminidase, hexosaminidase, beta-N-acetylgalactosaminidase and glucocerebrosidase have not been so widely studied as the beta-N-acetylhexosaminidases in bacteria, fungi and arthropods. Their biochemical role has been elucidated, however, and their urinary and plasma determination is being adopted for the early detection of diseases before clinical manifestation, in particular for hypertension, renal injuries and disorders, depression and lysosomal storage diseases. The spectrophotometric determinations of N-acetyl-beta-D-glucosaminidase, most often done with 3-cresolsulphone phthaleinyl N-acetyl-beta-D-glucosaminide, have been recently simplified and adapted to automatic instruments.
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PMID:Analytical biochemistry and clinical significance of N-acetyl-beta-D-glucosaminidase and related enzymes. 1090 64

A lysosomal storage disease (LSD) results from deficient lysosomal enzyme activity, thus the substrate of the mutant enzyme accumulates in the lysosome, leading to pathology. In many but not all LSDs, the clinically most important mutations compromise the cellular folding of the enzyme, subjecting it to endoplasmic reticulum-associated degradation instead of proper folding and lysosomal trafficking. A small molecule that restores partial mutant enzyme folding, trafficking, and activity would be highly desirable, particularly if one molecule could ameliorate multiple distinct LSDs by virtue of its mechanism of action. Inhibition of L-type Ca2+ channels, using either diltiazem or verapamil-both US Food and Drug Administration-approved hypertension drugs-partially restores N370S and L444P glucocerebrosidase homeostasis in Gaucher patient-derived fibroblasts; the latter mutation is associated with refractory neuropathic disease. Diltiazem structure-activity studies suggest that it is its Ca2+ channel blocker activity that enhances the capacity of the endoplasmic reticulum to fold misfolding-prone proteins, likely by modest up-regulation of a subset of molecular chaperones, including BiP and Hsp40. Importantly, diltiazem and verapamil also partially restore mutant enzyme homeostasis in two other distinct LSDs involving enzymes essential for glycoprotein and heparan sulfate degradation, namely alpha-mannosidosis and type IIIA mucopolysaccharidosis, respectively. Manipulation of calcium homeostasis may represent a general strategy to restore protein homeostasis in multiple LSDs. However, further efforts are required to demonstrate clinical utility and safety.
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PMID:Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis. 1825 60