. "2014-03-14+01:00"^^ . . . "0"^^ . . "Search of mechanisms responsible for adverse effects of amyloid beta on muscarinic receptor transmission."@en . " G-proteins" . "2016-12-31+01:00"^^ . . "0"^^ . . . " signal transmission" . "1"^^ . . "0"^^ . . . "0"^^ . . "muscarinic receptors, G-proteins, beta-amyloid, signal transmission, Alzheimer\u00B4s disease"@en . "Hled\u00E1n\u00ED mechanism\u016F \u0161kodliv\u00E9ho p\u016Fsoben\u00ED amyloidu beta na funkci muskarinov\u00FDch receptor\u016F." . "muscarinic receptors" . . "2014-01-01+01:00"^^ . . "http://www.isvav.cz/projectDetail.do?rowId=GA14-05696S"^^ . "Regular finding at autopsy in Alzheimer\u00B4s disease is loss of basal forebrain cholinergic neurons and damage of cerebral cortex cholinergic markers. In concert, the only approved drugs with limited benefit are cholinesterase inhibitors. We found in transgenic APPswe/PS1dE9 mouse model of the disease the early weakening of muscarinic signaling preceding amyloid deposition. It was not due to changes in muscarinic receptors or G-proteins expression, pointing to damage of receptor/G-protein interaction within membrane. The major obstacle in devising efficient therapy is a poor knowledge of likely reversible initial changes during the asymptomatic phase of the disease. The objective of this project is to identify mechanisms of initial muscarinic impairment by beta-amyloid. Knowledge of molecular mechanisms and time-course is of prime importance for development of new drugs and therapeutic strategies enabling proper selection of drug targets that are likely to depend on the stage of impairment but may not necessarily be confined to agents directly acting on muscarinic receptors."@en . "2015-04-23+02:00"^^ . . "GA14-05696S" . . . . . " beta-amyloid" . "Ztr\u00E1ta cholinergn\u00EDch neuron\u016F v baz\u00E1ln\u00EDm mozku a po\u0161kozen\u00ED cholinergn\u00EDch marker\u016F v mozkov\u00E9 k\u016F\u0159e jsou u Alzheimerovy nemoci pravideln\u00FDm patologick\u00FDm n\u00E1lezem post mortem. V souladu s t\u00EDmto n\u00E1lezem jsou inhibitory cholinester\u00E1z hlavn\u00ED z doposud schv\u00E1len\u00FDch av\u0161ak pouze omezen\u011B \u00FA\u010Dinn\u00FDch l\u00E9k\u016F. U my\u0161\u00EDho transgenn\u00EDho modelu onemocn\u011Bn\u00ED jsme zjistili oslabov\u00E1n\u00ED muskarinov\u00E9 transmise, kter\u00E9 p\u0159edch\u00E1zelo ukl\u00E1d\u00E1n\u00ED amyloidu a nebylo doprov\u00E1zeno zm\u011Bnami v expresi muskarinov\u00FDch receptor\u016F a s nimi interaguj\u00EDc\u00EDch G-protein\u016F. Tato pozorov\u00E1n\u00ED tedy ukazuj\u00ED na \u010Dasn\u00E9 po\u0161kozen\u00ED interakce muskarinov\u00FD receptor/G-protein v bun\u011B\u010Dn\u00E9 membr\u00E1n\u011B vlivem beta-amyloidu. Hlavn\u00ED p\u0159ek\u00E1\u017Ekou p\u0159i v\u00FDvoji \u00FA\u010Dinn\u00E9 l\u00E9\u010Dby je nedostate\u010Dn\u00E1 znalost po\u010D\u00E1te\u010Dn\u00EDch zm\u011Bn zp\u016Fsoben\u00FDch rozpustn\u00FDm beta-amyloidem, kter\u00E9 p\u0159edch\u00E1zej\u00ED o mnoho let symptomy onemocn\u011Bn\u00ED a jsou pravd\u011Bpodobn\u011B vratn\u00E9. Znalost molekul\u00E1rn\u00EDch mechanism\u016F a \u010Dasov\u00E9ho pr\u016Fb\u011Bhu po\u0161kozen\u00ED membr\u00E1ny, kter\u00E9 se nemus\u00ED t\u00FDkat pouze muskarinov\u00E9 transmise, je nezbytn\u00E1 pro v\u00FDvoj nov\u00FDch l\u00E9k\u016F a l\u00E9\u010Debn\u00FDch postup\u016F." .