PMC:4385177 / 21302-22753 JSONTXT

{"project":"2_test","denotations":[{"id":"25799108-15336960-2046594","span":{"begin":811,"end":813},"obj":"15336960"},{"id":"25799108-16102532-2046595","span":{"begin":858,"end":860},"obj":"16102532"},{"id":"25799108-22586365-2046596","span":{"begin":862,"end":864},"obj":"22586365"},{"id":"25799108-19909276-2046597","span":{"begin":866,"end":868},"obj":"19909276"},{"id":"25799108-17296551-2046598","span":{"begin":976,"end":978},"obj":"17296551"},{"id":"25799108-23260046-2046599","span":{"begin":980,"end":982},"obj":"23260046"},{"id":"25799108-20980592-2046600","span":{"begin":984,"end":986},"obj":"20980592"},{"id":"25799108-15878804-2046601","span":{"begin":1024,"end":1026},"obj":"15878804"},{"id":"25799108-16294323-2046602","span":{"begin":1028,"end":1030},"obj":"16294323"},{"id":"25799108-18183620-2046603","span":{"begin":1057,"end":1059},"obj":"18183620"},{"id":"25799108-21995941-2046604","span":{"begin":1437,"end":1439},"obj":"21995941"},{"id":"25799108-23201208-2046605","span":{"begin":1441,"end":1443},"obj":"23201208"},{"id":"25799108-23827309-2046606","span":{"begin":1445,"end":1447},"obj":"23827309"},{"id":"25799108-23748075-2046607","span":{"begin":1449,"end":1451},"obj":"23748075"}],"text":"This identification of variants in hippocalcin, an NCS protein detected in greatest abundance in the striatum, as the cause of a Mendelian form of dystonia suggests a role for perturbed calcium signaling in the pathogenesis of this condition. In terms of future research, it is important to note that NCS proteins, such as hippocalcin, possess no inherent enzymatic properties but exert their Ca2+-dependent functions through interactions with other proteins. Thus, the identification of downstream interactors is a necessary first step in understanding their specific activities. In the case of hippocalcin, the identity of its interactors remains incomplete. There is, nonetheless, evidence to suggest that it might have a role in (1) the modulation of cyclic nucleotide signaling in the olfactory epithelium,23 (2) long-term depression in the hippocampus,24, 25, 26 (3) generation of the slow afterhyperpolarization current (important in controlling neuronal excitability),27, 28, 29 (4) regulation of gene transcription,30, 31 and (5) neurite outgrowth.32 Although some other, currently unknown function of hippocalcin might underlie its involvement in dystonia, it is notable that, in relation to the processes mentioned above, both aberrant excitability of striatal neurons and altered synaptic plasticity due in part to decreased long-term depression are two mechanisms believed to be important in at least some forms of dystonia.33, 34, 35, 36"}