The Synaptic Protein Neuroligin-1 Interacts with the Amyloid β-Peptide. Is There a Role in Alzheimer's Disease?

Simple item page
dc.contributor.authorDinamarca, Margarita C.
dc.contributor.authorWeinstein, David
dc.contributor.authorMonasterio, Octavio
dc.contributor.authorInestrosa, Nibaldo C.
dc.date.accessioned2025-01-21T00:00:38Z
dc.date.available2025-01-21T00:00:38Z
dc.date.issued2011
dc.description.abstractAmyloid beta-peptide (A beta) is the main component of the amyloid plaques associated with Alzheimer's disease (AD). In the early steps of the disease soluble A beta 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 beta species in AD pathology, it is important to understand the mechanism by which A beta oligomers are targeted to synaptic junction. We report here the interaction between A beta 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 beta. Using intrinsic fluorescence and surface plasmon resonance, we found that A beta 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 beta was observed. A beta polymerization analysis-studied by thioflavin-T assay and electron microscopy-indicated that NL-1 stabilized A beta aggregates in vitro. Moreover, NL-1 acts as a nucleating factor during the A beta aggregation process, stimulating the formation of A beta oligomers. Besides, irnmunoprecipitation assays confirm that A beta oligomers interact with NL-1 but not with NL-2. In conclusion, our results show that NL-1 interacts with A beta increasing the formation of A beta oligomers, suggesting that this interaction could triggers the targeting of A beta oligomer to the postsynaptic regions of excitatory synapses.
dc.fechaingreso.objetodigital2025-01-21
dc.fuente.origenWOS
dc.identifier.doi10.1021/bi201246t
dc.identifier.issn0006-2960
dc.identifier.urihttps://doi.org/10.1021/bi201246t
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95350
dc.identifier.wosidWOS:000295058700004
dc.issue.numeroNo. 38
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final8137
dc.pagina.inicio8127
dc.revistaBiochemistry
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe Synaptic Protein Neuroligin-1 Interacts with the Amyloid β-Peptide. Is There a Role in Alzheimer's Disease?
dc.typeartículo
dc.volumen50
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
The Synaptic Protein Neuroligin-1 Interacts with the Amyloid β-Peptide. Is There a Role in Alzheimer’s Disease.pdf
Size:
192.81 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas