scholarly journals The therapeutic potential of chemical chaperones in protein folding diseases

Prion ◽  
2014 ◽  
Vol 8 (2) ◽  
pp. 197-202 ◽  
Author(s):  
Leonardo Cortez ◽  
Valerie Sim
Keyword(s):  
Protein Folding ◽  
Therapeutic Potential ◽  
Chemical Chaperones

scholarly journals The unfolded protein response in retinal vascular diseases: Implications and therapeutic potential beyond protein folding

2015 ◽  
Vol 45 ◽  
pp. 111-131 ◽  
Author(s):  
Sarah X. Zhang ◽  
Jacey H. Ma ◽  
Maulasri Bhatta ◽  
Steven J. Fliesler ◽  
Joshua J. Wang
Keyword(s):  
Protein Folding ◽  
Unfolded Protein Response ◽  
Therapeutic Potential ◽  
Vascular Diseases ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Chemical Chaperones: A Pharmacological Strategy for Disorders of Protein Folding and Trafficking

2002 ◽  
Vol 52 (6) ◽  
pp. 832-836 ◽  
Author(s):  
David H Perlmutter
Keyword(s):  
Protein Folding ◽  
Chemical Chaperones

scholarly journals Endoplasmic Reticulum Stress and Lipid Metabolism: Mechanisms and Therapeutic Potential

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Sana Basseri ◽  
Richard C. Austin
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Lipid Metabolism ◽  
Er Stress ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Stress Dependent

The endoplasmic reticulum (ER) plays a crucial role in protein folding, assembly, and secretion. Disruption of ER homeostasis may lead to accumulation of misfolded or unfolded proteins in the ER lumen, a condition referred to as ER stress. In response to ER stress, a signal transduction pathway known as the unfolded protein response (UPR) is activated. UPR activation allows the cell to cope with an increased protein-folding demand on the ER. Recent studies have shown that ER stress/UPR activation plays a critical role in lipid metabolism and homeostasis. ER-stress-dependent dysregulation of lipid metabolism may lead to dyslipidemia, insulin resistance, cardiovascular disease, type 2 diabetes, and obesity. In this paper, we examine recent findings illustrating the important role ER stress/UPR signalling pathways play in regulation of lipid metabolism, and how they may lead to dysregulation of lipid homeostasis.

scholarly journals Influence of molecular and chemical chaperones on protein folding

1996 ◽  
Vol 1 (2) ◽  
pp. 109 ◽  
Author(s):  
William J. Welch ◽  
C. Randell Brown
Keyword(s):  
Protein Folding ◽  
Chemical Chaperones

scholarly journals TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding

2021 ◽  
Vol 22 (18) ◽  
pp. 9998
Author(s):  
Jung Min Kim ◽  
Honggu Chun
Keyword(s):  
Protein Folding ◽  
Hela Cells ◽  
Intrinsically Disordered Proteins ◽  
Therapeutic Potential ◽  
Site Directed Mutagenesis ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Cellular Environment ◽  
Tar Rna ◽  
Hiv 1

The various effects of native protein folding on the stability and folding rate of intrinsically disordered proteins (IDPs) in crowded intracellular environments are important in biomedicine. Although most studies on protein folding have been conducted in vitro, providing valuable insights, studies on protein folding in crowded intracellular environments are scarce. This study aimed to explore the effects of intracellular molecular crowding on the folding of mutant transactivator HIV-1 Tat based on intracellular interactions, including TAR RNA, as proof of the previously reported chaperna-RNA concept. Considering that the Tat–TAR RNA motif binds RNA, we assessed the po tential function of TAR RNA as a chaperna for the refolding of R52Tat, a mutant in which the argi nine (R) residues at R52 have been replaced with alanine (A) by site-directed mutagenesis. We mon itored Tat-EGFP and Tat folding in HeLa cells via time-lapse fluorescence microscopy and biolayer interferometry using EGFP fusion as an indicator for folding status. These results show that the refolding of R52A Tat was stimulated well at a 0.3 μM TAR RNA concentration; wild-type Tat refolding was essentially abolished because of a reduction in the affinity for TAR RNA at that con centration. The folding and refolding of R52Tat were mainly promoted upon stimulation with TAR RNA. Our findings provide novel insights into the therapeutic potential of chaperna-mediated fold ing through the examination of as-yet-unexplored RNA-mediated protein folding as well as viral genetic variants that modulate viral evolutionary linkages for viral diseases inside a crowded intra cellular environment.

Characterization of the mechanisms by which missense mutations in the lysosomal acid lipase gene disrupt enzymatic activity

2019 ◽  
Vol 28 (18) ◽  
pp. 3043-3052 ◽  
Author(s):  
Terje Vinje ◽  
Jon K Laerdahl ◽  
Katrine Bjune ◽  
Trond P Leren ◽  
Thea Bismo Strøm
Keyword(s):  
Enzymatic Activity ◽  
Intracellular Transport ◽  
Therapeutic Potential ◽  
Missense Mutations ◽  
Acid Lipase ◽  
Lipase Gene ◽  
Mutant Proteins ◽  
Lysosomal Acid ◽  
Chemical Chaperones ◽  
Lysosomal Acid Lipase

Abstract Hydrolysis of cholesteryl esters and triglycerides in the lysosome is performed by lysosomal acid lipase (LAL). In this study we have investigated how 23 previously identified missense mutations in the LAL gene (LIPA) (OMIM# 613497) affect the structure of the protein and thereby disrupt LAL activity. Moreover, we have performed transfection studies to study intracellular transport of the 23 mutants. Our main finding was that most pathogenic mutations result in defective enzyme activity by affecting the normal folding of LAL. Whereas, most of the mutations leading to reduced stability of the cap domain did not alter intracellular transport, nearly all mutations that affect the stability of the core domain gave rise to a protein that was not efficiently transported from the endoplasmic reticulum (ER) to the Golgi apparatus. As a consequence, ER stress was generated that is assumed to result in ER-associated degradation of the mutant proteins. The two LAL mutants Q85K and S289C were selected to study whether secretion-defective mutants could be rescued from ER-associated degradation by the use of chemical chaperones. Of the five chemical chaperones tested, only the proteasomal inhibitor MG132 markedly increased the amount of mutant LAL secreted. However, essentially no increased enzymatic activity was observed in the media. These data indicate that the use of chemical chaperones to promote the exit of folding-defective LAL mutants from the ER, may not have a great therapeutic potential as long as these mutants appear to remain enzymatically inactive.

scholarly journals Unfolding the therapeutic potential of chemical chaperones for age-related macular degeneration

2008 ◽  
Vol 3 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Theodor Sauer ◽  
Mrinali Patel ◽  
Chi-Chao Chan ◽  
Jingsheng Tuo
Keyword(s):  
Macular Degeneration ◽  
Therapeutic Potential ◽  
Age Related Macular Degeneration ◽  
Chemical Chaperones ◽  
Age Related

Classification of Chemical Chaperones Based on Their Effect on Protein Folding Landscapes

2014 ◽  
Vol 10 (3) ◽  
pp. 813-820 ◽  
Author(s):  
Rohan Dandage ◽  
Anannya Bandyopadhyay ◽  
Gopal Gunanathan Jayaraj ◽  
Kanika Saxena ◽  
Vijit Dalal ◽  
...  
Keyword(s):  
Protein Folding ◽  
Chemical Chaperones
Sign in / Sign up

Export Citation Format

Share Document