c-Abl Deficiency Provides Synaptic Resiliency Against Aβ-Oligomers

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dc.contributor.authorGutierrez, Daniela A.
dc.contributor.authorVargas, Lina M.
dc.contributor.authorChandia-Cristi, America
dc.contributor.authorde la Fuente, Catalina
dc.contributor.authorLeal, Nancy
dc.contributor.authorAlvarez, Alejandra R.
dc.date.accessioned2025-01-23T21:09:01Z
dc.date.available2025-01-23T21:09:01Z
dc.date.issued2019
dc.description.abstractSpine pathology has been implicated in the early onset of Alzheimer & x2019;s disease (AD), where A & x3b2;-Oligomers (A & x3b2;Os) cause synaptic dysfunction and loss. Previously, we described that pharmacological inhibition of c-Abl prevents A & x3b2;Os-induced synaptic alterations. Hence, this kinase seems to be a key element in AD progression. Here, we studied the role of c-Abl on dendritic spine morphological changes induced by A & x3b2;Os using c-Abl null neurons (c-Abl-KO). First, we characterized the effect of c-Abl deficiency on dendritic spine density and found that its absence increases dendritic spine density. While A & x3b2;Os-treatment reduces the spine number in both wild-type (WT) and c-Abl-KO neurons, A & x3b2;Os-driven spine density loss was not affected by c-Abl. We then characterized A & x3b2;Os-induced morphological changes in dendritic spines of c-Abl-KO neurons. A & x3b2;Os induced a decrease in the number of mushroom spines in c-Abl-KO neurons while preserving the populations of immature stubby, thin, and filopodia spines. Furthermore, synaptic contacts evaluated by PSD95/Piccolo clustering and cell viability were preserved in A & x3b2;Os-exposed c-Abl-KO neurons. In conclusion, our results indicate that in the presence of A & x3b2;Os c-Abl participates in synaptic contact removal, increasing susceptibility to A & x3b2;Os damage. Its deficiency increases the immature spine population reducing A & x3b2;Os-induced synapse elimination. Therefore, c-Abl signaling could be a relevant actor in the early stages of AD.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fncel.2019.00526
dc.identifier.eissn1662-5102
dc.identifier.urihttps://doi.org/10.3389/fncel.2019.00526
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100796
dc.identifier.wosidWOS:000501844800001
dc.language.isoen
dc.revistaFrontiers in cellular neuroscience
dc.rightsacceso restringido
dc.subjectAlzheimer & x2019;s disease
dc.subjectc-Abl tyrosine kinase
dc.subjectsynapse
dc.subjectA beta-oligomers
dc.subjectdendritic spines
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlec-Abl Deficiency Provides Synaptic Resiliency Against Aβ-Oligomers
dc.typeartículo
dc.volumen13
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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