Linked Life Data

21838267

Source:http://linkedlifedata.com/resource/pubmed/id/21838267

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2011-9-20
pubmed:abstractText
Amyloid ?-peptide (A?) is the main component of the amyloid plaques associated with Alzheimer's disease (AD). In the early steps of the disease soluble A? oligomers are produced. According to the current "amyloid hypothesis" these oligomers can accumulate over time, leading progressively to the loss of synaptic function and the cognitive failure characteristic of AD. To understand the role of oligomeric A? species in AD pathology, it is important to understand the mechanism by which A? oligomers are targeted to synaptic junction. We report here the interaction between A? with neuroligin-1 (NL-1), a postsynaptic cell-adhesion protein specific for excitatory synapses, which shares a high degree of similarity with acetylcholinesterase, the first synaptic protein described to interact with A?. Using intrinsic fluorescence and surface plasmon resonance, we found that A? binds to the extracellular domain of NL-1 with a K(d) in the nanomolar range. In the case of NL-2, a postsynaptic cell-adhesion protein specific for inhibitory synapses, just a very weak interaction with A? was observed. A? polymerization analysis-studied by thioflavin-T assay and electron microscopy-indicated that NL-1 stabilized A? aggregates in vitro. Moreover, NL-1 acts as a nucleating factor during the A? aggregation process, stimulating the formation of A? oligomers. Besides, immunoprecipitation assays confirm that A? oligomers interact with NL-1 but not with NL-2. In conclusion, our results show that NL-1 interacts with A? increasing the formation of A? oligomers, suggesting that this interaction could triggers the targeting of A? oligomer to the postsynaptic regions of excitatory synapses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8127-37
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The synaptic protein neuroligin-1 interacts with the amyloid ?-peptide. Is there a role in Alzheimer's disease?
pubmed:affiliation
Centro de Envejecimiento y Regeneracio?n (CARE), Facultad de Ciencias Biolo?gicas, Pontificia Universidad Cato?lica de Chile, Santiago, Chile.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't