In lysosomal diseases, enzyme deficiency is caused by misfolding of mutant protein with abnormal steric structure that expressed gene mutation. Chaperone therapy a new molecular therapeutic approach primarily for diseases. The misfolded digested rapidly or aggregated to induce endoplasmic reticulum stress. As result, the catalytic activity lost. following sequence events results in chaperone ac...

Chaperones are produced by prokaryotic, yeast and higher eukaryotic cells for various purposes. Over-expression of each chaperone or sets of them affect the production level of a recombinant protein in the cell. On the basis of this hypothesis, five different plasmids with 5 different combinations of 6 chaperones molecule, transformed into Escherichia coli along with human basic Fibroblast Grow...

Chaperone therapy is a newly developed molecular therapeutic approach to protein misfolding diseases. Among them we found unstable mutant enzyme proteins in a few lysosomal diseases, resulting in rapid intracellular degradation and loss of function. Active-site binding low molecular competitive inhibitors (chemical chaperones) paradoxically stabilized and enhanced the enzyme activity in somatic...

Chaperones maintain a healthy proteome by preventing aggregation and by aiding in protein folding. Precisely how chaperones influence the conformational properties of their substrates, however, remains unclear. To achieve a detailed description of dynamic chaperone-substrate interactions, we fused site-specific NMR information with coarse-grained simulations. Our model system is the binding and...

RATIONALE Apoptosis and fatty acid-binding protein-4 (FABP4) induced-endoplasmic reticulum (ER) stress in macrophage is an important pathological process in several vascular occlusive diseases, including atherosclerosis, both of which are accelerated by lipids or inflammatory cytokines. OBJECTIVE To determine whether interleukin 17A (IL-17A) accelerates atherosclerosis through activating FABP...

Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins is a favorable method for amyloid disease treatment. Recently, chemical methods for protein reduction have been develo...

The heat shock protein Hsp33 is a very potent molecular chaperone with a distinctive mode of functional regulation; its activity is redox-regulated. In its reduced form all six cysteinyl residues of Hsp33 are present as thiols, and Hsp33 displays no folding helper activity. Exposure of Hsp33 to oxidizing conditions like H(2)O(2), however, rapidly converts Hsp33 into an efficient molecular chape...

Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that plays multiple roles in protein homeostasis. In these various tasks, the activity of Hsp70 is shaped by interactions with co-chaperones, such as Hsp40. The Hsp40 family of co-chaperones binds to Hsp70 through a conserved J-domain, and these factors stimulate ATPase and protein-folding activity. Using chemical screens, ...

Rationale: Asthma is a chronic inflammatory disease characterized by increased airway inflammation and fibrosis. So far, endoplasmic reticulum (ER) stress has been shown to play a role in several inflammatory diseases, however, its involvement in the pathogenesis of allergic asthma has not been clearly understood. It is also known that ER stress inhibitor chemical chaperone tauroursodeoxycholic...

Chaperone-mediated autophagy (CMA) contributes to cellular quality control and the cellular response to stress through the selective degradation of cytosolic proteins in lysosomes. A decrease in CMA activity occurs in aging and in age-related disorders (for example, neurodegenerative diseases and diabetes). Although prevention of this age-dependent decline through genetic manipulation in mice h...