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Cited by 27Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

Polo-like kinase 2 phosphorylation of amyloid precursor protein regulates activity-dependent amyloidogenic processing

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Lee, Yeunkum, Lee, Ji Soo, Lee, Kea Joo, Turner, R. Scott, Hoe, Hyang-Sook, Pak, Daniel T.S.·2017·Neuropharmacology
DOI 10.1016/j.neuropharm.2017.02.027PMC PMC5414040
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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits. Amyloidogenic processing of amyloid precursor protein (APP) produces amyloid β (Aβ), the major component of hallmark AD plaques. Synaptic activity stimulates APP cleavage, whereas APP promotes excitatory synaptic transmission, suggesting APP participates in neuronal homeostasis. However, mechanisms linking synaptic activity to APP processing are unclear. Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in vitro and associates with APP in vivo. Plk2 accelerates APP amyloidogenic cleavage by β-secretase at synapses and is required for neuronal overactivity-stimulated Aβ secretion. These findings implicate Plk2 as a novel mediator of activity-dependent APP amyloidogenic processing.

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  • PLK2 binds and phosphorylates Thr-668 and Ser-675 residues of amyloid precursor protein, which instigate Aβ production in hippocampal neurons, suggesting that PLK2 may be an important target molecule for AD treatment.

    “PLK2 (polo-like kinase 2) that binds and phosphorylates Thr-668 and Ser-675 residues of amyloid precursor protein, which instigate Aβ production in hippocampal neurons, suggesting that PLK2 may be an important target molecule for AD treatment [46].”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [46]

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Cited by

Sorted by citations

Authors
Lee, Y., Lee, J. S., Lee, K. J., Turner, R. S., Hoe, H.-S., & Pak, D. T. S.
Affiliations
  • Georgetown University (US)
  • Georgetown University Medical Center (US)
Corresponding author
Pak, Daniel T.S.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2017-05
Volume
117
Pages
387-400
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2017.02.027
PMC
PMC5414040
OpenAlex
W2594662124
Cited by
27
References
2
Citations by year
2026: 2 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 1
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Georgetown Memory Disorders Program, Georgetown Partners in Research (DTSP)
  • National Institute of Health (R01 NS048085, R03 AG052730)
  • NIH/NIC CCSG (P30-CA051008)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
PLK2, amyloid precursor protein, amyloid-beta, Alzheimer's disease, APP phosphorylation, beta-secretase, synaptic activity, homeostatic plasticity, APP cleavage
MeSH terms
Animals, Chlorocebus aethiops, Hippocampus, Humans, Mice, Inbred C57BL, Neurons, Phosphorylation, Protein Processing, Post-Translational, Synapses, Amyloid beta-Protein Precursor, Protein Serine-Threonine Kinases, Mice, Knockout, COS Cells, Rats

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