Pharmacological Chaperones: Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases

2016 ◽  
Vol 11 (6) ◽  
pp. 1471-1489 ◽  
Author(s):  
Marino Convertino ◽  
Jhuma Das ◽  
Nikolay V. Dokholyan
Keyword(s):  
Therapeutic Strategies ◽  
Design And Development ◽  
Conformational Diseases ◽  
Pharmacological Chaperones

scholarly journals Second-Generation Pharmacological Chaperones: Beyond Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3145 ◽  
Author(s):  
My Lan Tran ◽  
Yves Génisson ◽  
Stéphanie Ballereau ◽  
Cécile Dehoux
Keyword(s):  
Protein Misfolding ◽  
First Generation ◽  
Second Generation ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Pharmacological Chaperone ◽  
Conformational Diseases ◽  
Pharmacological Chaperones ◽  
Drug Candidates ◽  
Binding Pockets

Protein misfolding induced by missense mutations is the source of hundreds of conformational diseases. The cell quality control may eliminate nascent misfolded proteins, such as enzymes, and a pathological loss-of-function may result from their early degradation. Since the proof of concept in the 2000s, the bioinspired pharmacological chaperone therapy became a relevant low-molecular-weight compound strategy against conformational diseases. The first-generation pharmacological chaperones were competitive inhibitors of mutant enzymes. Counterintuitively, in binding to the active site, these inhibitors stabilize the proper folding of the mutated protein and partially rescue its cellular function. The main limitation of the first-generation pharmacological chaperones lies in the balance between enzyme activity enhancement and inhibition. Recent research efforts were directed towards the development of promising second-generation pharmacological chaperones. These non-inhibitory ligands, targeting previously unknown binding pockets, limit the risk of adverse enzymatic inhibition. Their pharmacophore identification is however challenging and likely requires a massive screening-based approach. This review focuses on second-generation chaperones designed to restore the cellular activity of misfolded enzymes. It intends to highlight, for a selected set of rare inherited metabolic disorders, the strategies implemented to identify and develop these pharmacologically relevant small organic molecules as potential drug candidates.

Pharmacological chaperones: potential treatment for conformational diseases

2004 ◽  
Vol 15 (5) ◽  
pp. 222-228 ◽  
Author(s):  
Virginie Bernier ◽  
Monique Lagacé ◽  
Daniel G Bichet ◽  
Michel Bouvier
Keyword(s):  
Potential Treatment ◽  
Conformational Diseases ◽  
Pharmacological Chaperones

scholarly journals New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

2015 ◽  
Vol 16 (12) ◽  
pp. 29446-29453 ◽  
Author(s):  
Ebbe Poulsen ◽  
Agnete Larsen ◽  
Alen Zollo ◽  
Arne Jørgensen ◽  
Kristian Sanggaard ◽  
...  
Keyword(s):  
Adaptor Protein ◽  
Therapeutic Strategies ◽  
Design And Development

A case study on use of personas in design and development of an audit management system

2007 ◽  
Author(s):  
Pallavi Dharwada ◽  
Joel S. Greenstein ◽  
Anand K. Gramopadhye ◽  
Steve J. Davis
Keyword(s):  
Management System ◽  
Design And Development ◽  
Audit Management

Design and development of a torque tool testing rig that simulates human operator-tool-task interactions

2010 ◽  
Author(s):  
Haluk Ay ◽  
Anthony Luscher ◽  
Carolyn Sommerich
Keyword(s):  
Human Operator ◽  
Design And Development ◽  
Tool Testing

Therapeutic strategies and techniques in early cognitive-behavioral therapy.

Psychotherapy ◽  
2019 ◽  
Vol 56 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Brittany R. King ◽  
James F. Boswell
Keyword(s):  
Cognitive Behavioral Therapy ◽  
Behavioral Therapy ◽  
Therapeutic Strategies ◽  
Cognitive Behavioral
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