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Pin1 mediates Ab42-mediated dendritic spine loss

ABSTRACT: Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in the neocortex of the brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration and likely contributes to synaptic loss, memory impairment, and behavioral changes in patients. Studies suggest that spine loss is induced by soluble, multimeric Ab42, whose post-synaptic signaling activates the protein phosphatase calcineurin. We investigated how calcineurin causes spine pathology and found that the cis-trans prolyl isomerase Pin1 is a critical downstream target of Ab42/calcineurin signaling. In spines, Pin1 interacts with and is dephosphorylated by calcineurin, which rapidly suppresses its isomerase activity. Pin1 knockout or Ab42 exposure induced mature spine loss in Ab42-treated wild-type cells but had no effect on Pin1 null neurons. The data implicate Pin1 in spine maintenance and synaptic loss in early Alzheimer's disease.

INSTRUMENT(S): orbitrap fusion lumos

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: James S. Malter

PROVIDER: MSV000082066 | MassIVE | Wed Feb 14 11:11:00 GMT 2018

REPOSITORIES: MassIVE

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