Pharmacological Chaperone Therapy for Pompe Disease [PDF]
Molecules, 2021 Pompe disease (PD), a lysosomal storage disease, is caused by mutations of the GAA gene, inducing deficiency in the acid alpha-glucosidase (GAA). This enzymatic impairment causes glycogen burden in lysosomes and triggers cell malfunctions, especially in ...
Yves Génisson +2 more
exaly +8 more sources
Second-Generation Pharmacological Chaperones: Beyond Inhibitors [PDF]
Molecules, 2020 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 ...
Yves Génisson +2 more
exaly +6 more sources
sp2-Iminosugars targeting human lysosomal β-hexosaminidase as pharmacological chaperone candidates for late-onset Tay-Sachs disease [PDF]
Journal of Enzyme Inhibition and Medicinal Chemistry, 2022 The late-onset form of Tay-Sachs disease displays when the activity levels of human β-hexosaminidase A (HexA) fall below 10% of normal, due to mutations that destabilise the native folded form of the enzyme and impair its trafficking to the lysosome ...
Manuel González-Cuesta +8 more
doaj +2 more sources
A Pharmacological Chaperone Therapy for Acute Intermittent Porphyria [PDF]
Molecular Therapy, 2020 Mutations in hydroxymethylbilane synthase (HMBS) cause acute intermittent porphyria (AIP), an autosomal dominant disease where typically only one HMBS allele is mutated. In AIP, the accumulation of porphyrin precursors triggers life-threatening neurovisceral attacks and at long-term, entails an increased risk of hepatocellular carcinoma, kidney failure,
Caroline Schmitt +2 more
exaly +7 more sources
Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis [PDF]
Molecules, 2022 GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; GLB1; E.C. 3.2.1.23), responsible for the hydrolysis of terminal β-galactosyl residues from GM1 ganglioside, glycoproteins, and ...
Francesca Clemente +8 more
doaj +2 more sources
Pharmacological chaperone action in humanized mouse models of MC4R-linked obesity [PDF]
JCI Insight, 2021 MC4R mutations represent the largest monogenic cause of obesity, resulting mainly from receptor misfolding and intracellular retention by the cellular quality control system. The present study aimed at determining whether pharmacological chaperones (PCs)
Patricia René +3 more
doaj +2 more sources
Design of a New α-1-C-Alkyl-DAB Derivative Acting as a Pharmacological Chaperone for β-Glucocerebrosidase Using Ligand Docking and Molecular Dynamics Simulation [PDF]
Molecules, 2018 Some point mutations in β-glucocerebrosidase cause either improper folding or instability of this protein, resulting in Gaucher disease. Pharmacological chaperones bind to the mutant enzyme and stabilize this enzyme; thus, pharmacological chaperone ...
Izumi Nakagome +6 more
doaj +2 more sources
Protein structural features predict responsiveness to pharmacological chaperone treatment for three lysosomal storage disorders. [PDF]
PLoS Computational Biology, 2021 Three-dimensional structures of proteins can provide important clues into the efficacy of personalized treatment. We perform a structural analysis of variants within three inherited lysosomal storage disorders, comparing variants responsive to ...
Jaie Woodard, Wei Zheng, Yang Zhang
doaj +2 more sources
Pharmacological chaperone reshapes the energy landscape for folding and aggregation of the prion protein [PDF]
Nature Communications, 2016 Small-molecule chaperones that can prevent protein misfolding have potential applications for treating diseases such as Alzheimer’s and ALS. Here the authors use high-resolution force spectroscopy to gain insight into the mechanism of action of an iron ...
Amar Nath Gupta +5 more
doaj +2 more sources
Structure-Activity Relationships of Dopamine Transporter Pharmacological Chaperones
Frontiers in Cellular Neuroscience, 2022 Mutations in the dopamine transporter gene (SLC6A3) have been implicated in many human diseases. Among these is the infantile parkinsonism-dystonia known as Dopamine Transporter Deficiency Syndrome (DTDS).
Charles Sutton +12 more
doaj +1 more source