Linked Life Data

21116052

Source:http://linkedlifedata.com/resource/pubmed/id/21116052

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-28
pubmed:abstractText
Amyloid-? (A?) peptides in the brain of patients with Alzheimer's disease (AD) assemble into various aggregation forms that differ in size, structure, and functional properties. Previous studies have shown that A? binds to nicotinic acetylcholine receptors (nAChRs) and activates signaling cascades that result in the disruption of synaptic functions. These findings suggest a possible link between impaired cholinergic neurotransmitter function in AD and A? pathogenesis. However, it is not yet known how the different A? assemblies interact with specific nAChR subtypes. In the present study, we demonstrate that neurotoxicity in neuronal cells in culture induced by fibrillar A?(1-40) is prevented through an ?7 nAChR-dependent mechanism. The ?7 nAChR agonists varenicline and JN403 increased binding of the amyloid ligand [³H]PIB to fibrillar A? in AD frontal cortex autopsy tissue. This suggests that the presence of nAChR agonists may inhibit interaction of A? with ?7 nAChRs and prevent the formation of A?/?7 nAChR complexes. This interaction was confirmed in binding assays with [¹²?I]A?(1-40) and ?7 nAChRs in autopsy brain tissue homogenates from the frontal cortex. The functional effects of A? fibrils and oligomers on nAChRs were examined by measuring intracellular calcium ([Ca(2+)](i) levels. Oligomeric, but not fibrillar A?(1-40), increased [Ca(2+)](i) in neuronal cells, and this effect was attenuated by varenicline. Our findings demonstrate that fibrillar A? exerts neurotoxic effects mediated partly through a blockade of ?7 nAChRs, whilst oligomeric A? may act as a ligand activating ?7 nAChRs, thereby stimulating downstream signaling pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1875-8908
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
335-47
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Functional interactions of fibrillar and oligomeric amyloid-? with alpha7 nicotinic receptors in Alzheimer's disease.
pubmed:affiliation
Karolinska Institutet, Division of Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't