Pin1 mediates Aβ42-induced dendritic spine loss

Nancy R. Stallings, Melissa A. O'Neal, Jie Hu, Ege T. Kavalali, Ilya Bezprozvanny, James S. Malter

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 dendritic spine loss is induced by soluble, multimeric amyloid-β (A?β2), which, through postsynaptic signaling, activates the protein phosphatase calcineurin. We investigated how calcineurin caused spine pathology and found that the cis-Trans prolyl isomerase Pin1 was a critical downstream target of Aβ42-calcineurin signaling. In dendritic spines, Pin1 interacted with and was dephosphorylated by calcineurin, which rapidly suppressed its isomerase activity. Knockout of Pin1 or exposure to A?42 induced the loss of mature dendritic spines, which was prevented by exogenous Pin1. The calcineurin inhibitor FK506 blocked dendritic spine loss in Aβ42-Treated wild-Type cells but had no effect on Pin1-null neurons. These data implicate Pin1 in dendritic spine maintenance and synaptic loss in early Alzheimer's disease.

Original languageEnglish (US)
Article numbereaap8734
JournalScience Signaling
Volume11
Issue number522
DOIs
StatePublished - Mar 20 2018

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Dendritic Spines
Calcineurin
Pathology
cis-trans-Isomerases
Alzheimer Disease
Peptidylprolyl Isomerase
Isomerases
Phosphoprotein Phosphatases
Neocortex
Memory Disorders
Tacrolimus
Amyloid
Neurons
Brain
Spine
Maintenance
Data storage equipment

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Pin1 mediates Aβ42-induced dendritic spine loss. / Stallings, Nancy R.; O'Neal, Melissa A.; Hu, Jie; Kavalali, Ege T.; Bezprozvanny, Ilya; Malter, James S.

In: Science Signaling, Vol. 11, No. 522, eaap8734, 20.03.2018.

Research output: Contribution to journalArticle

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AU - Malter, James S.

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