" MITOCHONDRIA" . . . . . "THE MECHANISMS UNDERLYING THE PATHOLOGICAL EFFECTS OF APOE4 IN ALZHEIMER\u2019S DISEASE AND THEIR NEURONAL SPECIFICITY"@en . "LH13269" . . . . "2013-03-01+01:00"^^ . " AMYLOID-BETA" . . " APOE4" . . . "2015-02-16+01:00"^^ . . "V\u00FDzkum mechanizm\u016F zodpov\u011Bdn\u00FDch za neuropatologick\u00E9 \u00FA\u010Dinky a neuron\u00E1ln\u00ED specificitu apolipoproteinu E4" . "2014-02-28+01:00"^^ . "Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor of Alzheimer\u2019s disease (AD). The overall objective of this proposal is to investigate the cellular and molecular mechanisms underlying the neuronal and synaptic effects of apoE4 and their neuronal specificity: This will first be pursued by an hypothesis driven approach, which stems from our preliminary results, and will focus on the hypothesis that A\u03B2 tau and mitochondria mediate the neuron specific effects of apoE4. The possible role of additional mechanisms will be investigated by nonbiased proteomic analysis of the effects of apoE4 on the levels and repertoire of synaptic proteins in distinct cholinergic and glutamatergic nerve terminals. This study is expected to further the understanding of the mechanisms underlying neuronal specificity of neurodegeneration in AD. Furthermore, the insight to be gained is expected to have important medical applications and to assist in the design and development of novel therapeutic strategies."@en . . . . . "2015-02-28+01:00"^^ . "0"^^ . "Apolipoprotein E4 je nejd\u016Fle\u017Eit\u011Bj\u0161\u00ED geneticky dan\u00FD rizikov\u00FD faktor Alzheimerovy nemoci. Smyslem tohoto projektu je objasn\u011Bn\u00ED bun\u011B\u010Dn\u00FDch a molekul\u00E1rn\u00EDch mechanizm\u016F, kter\u00E9 se uplat\u0148uj\u00ED p\u0159i jeho \u0161kodliv\u00FDch \u00FA\u010Dinc\u00EDch na synapse a na citlivosti r\u016Fzn\u00FDch neuron\u00E1ln\u00EDch populac\u00ED v\u016F\u010Di jeho p\u016Fsoben\u00ED. Znalost mechanizm\u016F \u00FA\u010Dinku ApoE4 je d\u016Fle\u017Eit\u00E1 pro navrhov\u00E1n\u00ED l\u00E9\u010Dby onemocn\u011Bn\u00ED. Pro dosa\u017Een\u00ED t\u011Bchto c\u00EDl\u016F vyu\u017Eijeme dva p\u0159\u00EDstupy. Prvn\u00ED vych\u00E1z\u00ED z na\u0161ich p\u0159edb\u011B\u017En\u00FDch v\u00FDsledk\u016F a hypot\u00E9zy, \u017Ee \u0161kodliv\u00E9 \u00FA\u010Dinky ApoE4 na ur\u010Dit\u00E9 populace neuron\u016F zprost\u0159edkov\u00E1v\u00E1 amyloid beta, protein tau a po\u0161kozen\u00ED funkce mitochondri\u00ED. Druh\u00FD, nezat\u00ED\u017Een\u00FD, p\u0159\u00EDstup bude pomoc\u00ED proteomick\u00E9 anal\u00FDzy zkoumat zm\u011Bny v koncentraci a zastoupen\u00ED synaptick\u00FDch proteinov\u00FDch marker\u016F posti\u017Een\u00FDch cholinergn\u00EDch a glutam\u00E1tergn\u00EDch synaps\u00ED. Vyu\u017Eijeme komplement\u00E1rn\u00EDch metod, pou\u017E\u00EDvan\u00FDch na pracovi\u0161ti v Izraeli (imunocytochemie, konfok\u00E1ln\u00ED mikroskopie, proteomick\u00E1 anal\u00FDza) a \u010Cesk\u00E9 republice (funk\u010Dn\u00ED pokusy s intaktn\u00ED tk\u00E1n\u00ED ex vivo, fyziologie a farmakologie receptor\u016F)." . . " TAU" . " SYNAPTIC TRANSMISSION" . "0"^^ . "1"^^ . "0"^^ . "0"^^ . . "ALZHEIMER\u2019S DISEASE; APOE4; SYNAPTIC TRANSMISSION; AMYLOID-BETA; TAU; MITOCHONDRIA; TRANSGENIC MICE"@en . "http://www.isvav.cz/projectDetail.do?rowId=LH13269"^^ . "ALZHEIMER\u2019S DISEASE" .