Compounds > 4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione

4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione and Myotonic-Dystrophy

4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione has been researched along with Myotonic-Dystrophy* in 2 studies

Other Studies

2 other study(ies) available for 4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione and Myotonic-Dystrophy

Article	Year
Correction of GSK3β at young age prevents muscle pathology in mice with myotonic dystrophy type 1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018, Volume: 32, Issue:4 Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1 (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and alter CUGBP1 activity via a glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA, containing long repeats ( HSA Topics: Animals; CELF1 Protein; Cells, Cultured; Enzyme Inhibitors; Female; Glycogen Synthase Kinase 3 beta; Humans; Male; Mice; Muscle Development; Muscle, Skeletal; Myotonic Dystrophy; Thiadiazoles	2018
GSK3β mediates muscle pathology in myotonic dystrophy. The Journal of clinical investigation, 2012, Volume: 122, Issue:12 Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease characterized by skeletal muscle wasting, weakness, and myotonia. DM1 is caused by the accumulation of CUG repeats, which alter the biological activities of RNA-binding proteins, including CUG-binding protein 1 (CUGBP1). CUGBP1 is an important skeletal muscle translational regulator that is activated by cyclin D3-dependent kinase 4 (CDK4). Here we show that mutant CUG repeats suppress Cdk4 signaling by increasing the stability and activity of glycogen synthase kinase 3β (GSK3β). Using a mouse model of DM1 (HSA(LR)), we found that CUG repeats in the 3' untranslated region (UTR) of human skeletal actin increase active GSK3β in skeletal muscle of mice, prior to the development of skeletal muscle weakness. Inhibition of GSK3β in both DM1 cell culture and mouse models corrected cyclin D3 levels and reduced muscle weakness and myotonia in DM1 mice. Our data predict that compounds normalizing GSK3β activity might be beneficial for improvement of muscle function in patients with DM1. Topics: Adult; Animals; CHO Cells; Cricetinae; Cyclin D3; Enzyme Stability; Female; Gene Expression Regulation, Enzymologic; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Lithium; Male; Mice; Middle Aged; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Myotonic Dystrophy; Phosphorylation; Protein Processing, Post-Translational; Thiadiazoles	2012

Article

Year

Correction of GSK3β at young age prevents muscle pathology in mice with myotonic dystrophy type 1.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018, Volume: 32, Issue:4

Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1 (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and alter CUGBP1 activity via a glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA, containing long repeats ( HSA

Topics: Animals; CELF1 Protein; Cells, Cultured; Enzyme Inhibitors; Female; Glycogen Synthase Kinase 3 beta; Humans; Male; Mice; Muscle Development; Muscle, Skeletal; Myotonic Dystrophy; Thiadiazoles

2018

GSK3β mediates muscle pathology in myotonic dystrophy.

The Journal of clinical investigation, 2012, Volume: 122, Issue:12

Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease characterized by skeletal muscle wasting, weakness, and myotonia. DM1 is caused by the accumulation of CUG repeats, which alter the biological activities of RNA-binding proteins, including CUG-binding protein 1 (CUGBP1). CUGBP1 is an important skeletal muscle translational regulator that is activated by cyclin D3-dependent kinase 4 (CDK4). Here we show that mutant CUG repeats suppress Cdk4 signaling by increasing the stability and activity of glycogen synthase kinase 3β (GSK3β). Using a mouse model of DM1 (HSA(LR)), we found that CUG repeats in the 3' untranslated region (UTR) of human skeletal actin increase active GSK3β in skeletal muscle of mice, prior to the development of skeletal muscle weakness. Inhibition of GSK3β in both DM1 cell culture and mouse models corrected cyclin D3 levels and reduced muscle weakness and myotonia in DM1 mice. Our data predict that compounds normalizing GSK3β activity might be beneficial for improvement of muscle function in patients with DM1.

Topics: Adult; Animals; CHO Cells; Cricetinae; Cyclin D3; Enzyme Stability; Female; Gene Expression Regulation, Enzymologic; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Lithium; Male; Mice; Middle Aged; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Myotonic Dystrophy; Phosphorylation; Protein Processing, Post-Translational; Thiadiazoles

2012