Research ArticleNeurodegeneration

Pin1 mediates Aβ42-induced dendritic spine loss

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Science Signaling  20 Mar 2018:
Vol. 11, Issue 522, eaap8734
DOI: 10.1126/scisignal.aap8734

Pinpointing amyloid’s toxicity

An increase in the amount of amyloid-β (Aβ) in neurons alters calcium signaling and causes synaptic dysfunction and dendritic spine loss, which is believed to cause neurodegeneration and cognitive deficits in Alzheimer’s disease (AD). The decreased activity of Pin1, a protein that structurally alters the function of serine- and threonine-phosphorylated proteins (including amyloid precursor protein and tau in the postsynaptic space of neurons), is also associated with AD. Using mouse models of AD, Stallings et al. found that Pin1 was dephosphorylated and inactivated by the calcium-dependent phosphatase calcineurin, whose activity in postsynaptic neurons was induced by Aβ. Aβ-induced spine loss was prevented by treating mice with the calcineurin inhibitor FK506 (also known as tacrolimus), an immunosuppressant used to reduce the rejection of organ transplants, suggesting that this drug might be repurposed to treat patients with AD.

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