Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-20
pubmed:abstractText
The cellular pathology of Alzheimer's disease is progressive and protracted leading eventually to considerable neuronal death. The underlying mechanisms of the pathology are complex but changes in the control of intracellular Ca2+ are believed to contribute to the demise of neurons. In this study, we investigated the functional consequences of an increase in the expression of the type 3 isoform of the ryanodine receptor (RyR3). We found that although cortical neurons from TgCRND8 mice secreted significantly more amyloid beta protein and showed significantly increased RyR3 expression, they were no more sensitive to cell stress than non-transgenic neurons. Furthermore, despite increased intracellular Ca2+ release in response to ryanodine, we found that basal Ca2+, K+-evoked Ca2+ responses, and capacitative Ca2+ entry were no different in TgCRND8 neurons compared with non-transgenic neurons. Therefore, as RyR3 up-regulation did not affect neuronal health or global Ca2+ homeostasis, we investigated the effect of reducing RyR3 expression using small interfering RNA. Surprisingly, a reduction of RyR3 expression in TgCRND8, but not in non-transgenic, neurons increased neuronal death. These data reveal a new role for RyR3 and indicate a novel potential therapeutic target to delay or prevent the progression of Alzheimer's disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Phosphopyruvate Hydratase, http://linkedlifedata.com/resource/pubmed/chemical/Potassium, http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine Receptor Calcium Release..., http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-40), http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42), http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein, http://linkedlifedata.com/resource/pubmed/chemical/thiazolyl blue
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
356-65
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19903243-Alzheimer Disease, pubmed-meshheading:19903243-Amyloid beta-Peptides, pubmed-meshheading:19903243-Amyloid beta-Protein Precursor, pubmed-meshheading:19903243-Animals, pubmed-meshheading:19903243-Calcium, pubmed-meshheading:19903243-Cell Death, pubmed-meshheading:19903243-Cells, Cultured, pubmed-meshheading:19903243-Cerebral Cortex, pubmed-meshheading:19903243-Disease Models, Animal, pubmed-meshheading:19903243-Dose-Response Relationship, Drug, pubmed-meshheading:19903243-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19903243-Glutamic Acid, pubmed-meshheading:19903243-Green Fluorescent Proteins, pubmed-meshheading:19903243-Humans, pubmed-meshheading:19903243-Mice, pubmed-meshheading:19903243-Mice, Transgenic, pubmed-meshheading:19903243-Mutation, pubmed-meshheading:19903243-Neurons, pubmed-meshheading:19903243-Peptide Fragments, pubmed-meshheading:19903243-Phosphopyruvate Hydratase, pubmed-meshheading:19903243-Potassium, pubmed-meshheading:19903243-Presenilin-1, pubmed-meshheading:19903243-RNA, Messenger, pubmed-meshheading:19903243-RNA, Small Interfering, pubmed-meshheading:19903243-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:19903243-Tetrazolium Salts, pubmed-meshheading:19903243-Thiazoles, pubmed-meshheading:19903243-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Up-regulation of the type 3 ryanodine receptor is neuroprotective in the TgCRND8 mouse model of Alzheimer's disease.
pubmed:affiliation
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't