Alzheimer's Disease, Dendritic Spines, and Calcineurin Inhibitors: A New Approach?

Melissa A. O'Neal, Nancy R. Stallings, James S. Malter

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Therapeutics to effectively treat Alzheimer's disease (AD) are lacking. In vitro, animal and human studies have implicated the excessive activation of the protein phosphatase calcineurin (CN) as an early step in the pathogenesis of AD. We discuss recent data showing that the prolyl isomerase Pin1 is suppressed by CN-mediated dephosphorylation induced by Aβ42 signaling. Pin1 loss directly leads to the reductions in dendritic spines and synapses characteristic of early AD pathology. Pin1 activity, and synapse and dendritic spine numbers are rescued by FK506, a highly specific and United States Food and Drug Administration approved CN inhibitor. Solid organ transplant recipients chronically treated with FK506 showed much lower AD incidence than expected. As such, we suggest prospective clinical trials to determine if systemic FK506 can normalize CN activity in the brain, preserve Pin1 function and support synaptic health in early AD.

Original languageEnglish (US)
Pages (from-to)1233-1234
Number of pages2
JournalACS Chemical Neuroscience
Volume9
Issue number6
DOIs
StatePublished - Jun 20 2018

Fingerprint

Dendritic Spines
Alzheimer Disease
Calcineurin
Tacrolimus
Synapses
Peptidylprolyl Isomerase
Transplants
Phosphoprotein Phosphatases
Pathology
United States Food and Drug Administration
Brain
Animals
Chemical activation
Calcineurin Inhibitors
Health
Clinical Trials
Incidence

Keywords

  • Alzheimer's disease
  • calcineurin
  • dendritic spines
  • FK506
  • Pin1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Cite this

Alzheimer's Disease, Dendritic Spines, and Calcineurin Inhibitors : A New Approach? / O'Neal, Melissa A.; Stallings, Nancy R.; Malter, James S.

In: ACS Chemical Neuroscience, Vol. 9, No. 6, 20.06.2018, p. 1233-1234.

Research output: Contribution to journalReview article

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