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Cited by 66Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsConnective Tissue Growth Factor Research

Wnt1 Inducible Signaling Pathway Protein 1 (WISP1) Targets PRAS40 to Govern β-Amyloid Apoptotic Injury of Microglia

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Chen Shang, Yan, Zhong Chong, Zhao, Wang, Shaohui, Maiese, Kenneth·2012·Current Neurovascular Research
DOI 10.2174/156720212803530618PMC PMC3521866
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Abstract

Given the present challenges to attain effective treatment for β-amyloid (Aβ) toxicity in neurodegenerative disorders such as Alzheimer's disease, development of novel cytoprotective pathways that can assist immune mediated therapies through the preservation of central nervous system microglia could offer significant promise. We show that the CCN4 protein, Wnt1 inducible signaling pathway protein 1 (WISP1), is initially up-regulated by Aβ and can modulate its endogenous expression for the protection of microglia during Aβ mediated apoptosis. WISP1 activates mTOR and phosphorylates p70S6K and 4EBP1 through the control of the regulatory mTOR component PRAS40. Loss of PRAS40 through gene reduction or inhibition by WISP1 is cytoprotective. WISP1 ultimately governs PRAS40 by sequestering PRAS40 intracellularly through post-translational phosphorylation and binding to protein 14-3-3. Our work identifies WISP1, mTOR signaling, and PRAS40 as targets for new strategies directed against Alzheimer's disease and related disorders.

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Cited by

Sorted by citations

Authors
Chen Shang, Y., Zhong Chong, Z., Wang, S., & Maiese, K.
Affiliations
Rutgers Cancer Institute (US)
Corresponding author
Maiese, Kenneth
ORCID
Venue
Current Neurovascular Research
Publisher
Bentham Science Publishers Ltd.
Published
2012-10-01
Volume
9
Issue
4
Pages
239-249
ISSN
1567-2026 (ISSN-L)
DOI
10.2174/156720212803530618
PMC
PMC3521866
OpenAlex
W2155738520
Cited by
66
References
6
Citations by year
2026: 4 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 3
FWCI
3.86
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Current Neurovascular Research (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Diabetes Association
  • American Heart Association
  • National Institutes of Health
  • National Institute on Aging
  • National Institute of Neurological Disorders and Stroke (R01NS053946)
  • National Institute of Environmental Health Sciences
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Keywords
WISP1, CCN4, PRAS40, amyloid-beta, microglia, apoptosis, Alzheimer's disease, mTOR signaling, p70S6K, 4E-BP1, post-translational phosphorylation, neuroprotection, neuroinflammation
MeSH terms
Cell Line, Humans, Intracellular Fluid, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Random Allocation, Up-Regulation, Amyloid beta-Peptides, Apoptosis, Microglia, Adaptor Proteins, Signal Transducing, CCN Intercellular Signaling Proteins

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