| pubmed-article:20573903 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20573903 | lifeskim:mentions | umls-concept:C0006675 | lld:lifeskim |
| pubmed-article:20573903 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:20573903 | lifeskim:mentions | umls-concept:C0521390 | lld:lifeskim |
| pubmed-article:20573903 | lifeskim:mentions | umls-concept:C0872078 | lld:lifeskim |
| pubmed-article:20573903 | lifeskim:mentions | umls-concept:C0019868 | lld:lifeskim |
| pubmed-article:20573903 | pubmed:issue | 25 | lld:pubmed |
| pubmed-article:20573903 | pubmed:dateCreated | 2010-6-24 | lld:pubmed |
| pubmed-article:20573903 | pubmed:abstractText | Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca(2+)) signaling abnormalities. To explain these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passive Ca(2+) leak channels. To directly investigate the role of presenilins in neuronal ER Ca(2+) homeostasis, we here performed a series of Ca(2+) imaging experiments with primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/-)) and from triple-transgenic AD mice (KI-PS1(M146V), Thy1-APP(KM670/671NL), Thy1-tau(P301L)). Obtained results provided additional support to the hypothesis that presenilins function as ER Ca(2+) leak channels in neurons. Interestingly, we discovered that presenilins play a major role in ER Ca(2+) leak function in hippocampal but not in striatal neurons. We further discovered that, in hippocampal neurons, loss of presenilin-mediated ER Ca(2+) leak function was compensated by an increase in expression and function of ryanodine receptors (RyanRs). Long-term feeding of the RyanR inhibitor dantrolene to amyloid precursor protein-presenilin-1 mice (Thy1-APP(KM670/671NL), Thy1-PS1(L166P)) resulted in an increased amyloid load, loss of synaptic markers, and neuronal atrophy in hippocampal and cortical regions. These results indicate that disruption of ER Ca(2+) leak function of presenilins may play an important role in AD pathogenesis. | lld:pubmed |
| pubmed-article:20573903 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20573903 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20573903 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20573903 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20573903 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20573903 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20573903 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20573903 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20573903 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20573903 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:20573903 | pubmed:issn | 1529-2401 | lld:pubmed |
| pubmed-article:20573903 | pubmed:author | pubmed-author:De... | lld:pubmed |
| pubmed-article:20573903 | pubmed:author | pubmed-author:BezprozvannyI... | lld:pubmed |
| pubmed-article:20573903 | pubmed:author | pubmed-author:ZhangHuaH | lld:pubmed |
| pubmed-article:20573903 | pubmed:author | pubmed-author:HerremanAnA | lld:pubmed |
| pubmed-article:20573903 | pubmed:author | pubmed-author:SunSuyaS | lld:pubmed |
| pubmed-article:20573903 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20573903 | pubmed:day | 23 | lld:pubmed |
| pubmed-article:20573903 | pubmed:volume | 30 | lld:pubmed |
| pubmed-article:20573903 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20573903 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20573903 | pubmed:pagination | 8566-80 | lld:pubmed |
| pubmed-article:20573903 | pubmed:dateRevised | 2011-3-3 | lld:pubmed |
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| pubmed-article:20573903 | pubmed:meshHeading | pubmed-meshheading:20573903... | lld:pubmed |
| pubmed-article:20573903 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20573903 | pubmed:articleTitle | Role of presenilins in neuronal calcium homeostasis. | lld:pubmed |
| pubmed-article:20573903 | pubmed:affiliation | Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA. | lld:pubmed |
| pubmed-article:20573903 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20573903 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:20573903 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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