Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder.

Intracellular calcium is a powerful secondary messenger that affects a number of calcium sensors, including calpain, a Ca2+-dependent cysteine protease, and calcineurin, a Ca2+/calmodulin-dependent protein phosphatase. Maintenance of low basal levels of intracellular calcium allows for the tightly regulated physiological activation of these proteins, which is crucial to a wide variety of cellular processes, such as fertilization, proliferation, development, learning, and memory. Deregulation of calpain and calcineurin has been implicated in the pathogenesis of several disorders, including hypertension, heart disease, diabetes, cerebral ischemia, and Alzheimer's disease. Recent studies have demonstrated an interplay between calpain and calcineurin, in which calpain can directly regulate calcineurin activity through proteolysis in glutamate-stimulated neurons in culture and in vivo. The calpain-mediated proteolytic cleavage of calcineurin increases phosphatase activity, which promotes caspase-mediated neuronal cell death. Thus, the activation of the calpain-calcineurin pathway could contribute to calcium-dependent disorders, especially those associated with Alzheimer's disease and myocardial hypertrophy. Here, we focus briefly on recent advances in revealing the structural and functional properties of these 2 calcium-activated proteins, as well as on the interplay between the 2, in an effort to understand how calpain-calcineurin signaling may relate to the pathogenesis of calcium- dependent disorders

6-Amino-8-(2-bromo­phen­yl)-1,7,8,8a-tetrahydro-3H-isothio­chromene-5,7,7-tricarbonitrile dimethyl­formamide solvate

In the title compound, C18H13BrN4S·C3H7NO, the thio­pyran ring and the adjacent six-numbered ring adopt distorted boat conformations. The mol­ecules, lying about inversion centers, form hydrogen-bonded dimers involving one of the H atoms on the amino group with the N atom of a cyano group of an adjacent mol­ecule, resulting in a 12-membered ring system [R 2 2(12) ring motif]. The other H atom of the amino group forms an inter­molecular hydrogen bond with the O atom of the dimethyl­formamide (DMF) mol­ecule. Another lone pair of electrons on the same carbonyl O atom of DMF mol­ecule forms a non-classical C—H⋯O inter­molecular hydrogen bond, resulting in a chain of mol­ecules

(E)-Methyl 3-(3,4-dihy­droxy­phen­yl)acrylate

The benzene ring in the title compound, C10H10O4, makes an angle of 4.4 (1)° with the C—C—C—O linker. The hy­droxy groups are involved in both intra- and inter­molecular O—H⋯O hydrogen bonds. The crystal packing is stabilized by O—H⋯O hydrogen-bonding inter­actions. The mol­ecules of the caffeic acid ester form a dimeric structure in a head-to-head manner along the a axis through O—H⋯O hydrogen bonds. The dimers inter­act with one another through O—H⋯O hydrogen bonds, forming supermolecular chains. These chains are further extended through C—H⋯O hydrogen bonds as well as van der Waals inter­actions into the final three-dimensional architecture