k201-compound and Nephrotic-Syndrome

k201-compound has been researched along with Nephrotic-Syndrome* in 1 studies

Other Studies

1 other study(ies) available for k201-compound and Nephrotic-Syndrome

ArticleYear
Discovery of endoplasmic reticulum calcium stabilizers to rescue ER-stressed podocytes in nephrotic syndrome.
    Proceedings of the National Academy of Sciences of the United States of America, 2019, 07-09, Volume: 116, Issue:28

    Emerging evidence has established primary nephrotic syndrome (NS), including focal segmental glomerulosclerosis (FSGS), as a primary podocytopathy. Despite the underlying importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of NS, no treatment currently targets the podocyte ER. In our monogenic podocyte ER stress-induced NS/FSGS mouse model, the podocyte type 2 ryanodine receptor (RyR2)/calcium release channel on the ER was phosphorylated, resulting in ER calcium leak and cytosolic calcium elevation. The altered intracellular calcium homeostasis led to activation of calcium-dependent cytosolic protease calpain 2 and cleavage of its important downstream substrates, including the apoptotic molecule procaspase 12 and podocyte cytoskeletal protein talin 1. Importantly, a chemical compound, K201, can block RyR2-Ser2808 phosphorylation-mediated ER calcium depletion and podocyte injury in ER-stressed podocytes, as well as inhibit albuminuria in our NS model. In addition, we discovered that mesencephalic astrocyte-derived neurotrophic factor (MANF) can revert defective RyR2-induced ER calcium leak, a bioactivity for this ER stress-responsive protein. Thus, podocyte RyR2 remodeling contributes to ER stress-induced podocyte injury. K201 and MANF could be promising therapies for the treatment of podocyte ER stress-induced NS/FSGS.

    Topics: Albuminuria; Animals; Calcium; Calcium Signaling; Calpain; Disease Models, Animal; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Glomerulosclerosis, Focal Segmental; Humans; Mice; Nephrotic Syndrome; Nerve Growth Factors; Podocytes; Ryanodine Receptor Calcium Release Channel; Talin; Thiazepines

2019