sFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease

Warrier S 1 , Marimuthu R 2 , Sekhar S 3 , Bhuvanalakshmi G 3 , Arfuso F 4 , Das AK 5 Show all authors , Bhonde R 3 , Martins R 6 , Dharmarajan A 7

Affiliations 

  • 1 Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 065, India; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6845, Australia. Electronic address: sudha.warrier@manipal.edu
  • 2 Department of Orthopedics, Sree Balaji Medical College and Hospital, Chromepet, Chennai 600044, India
  • 3 Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 065, India
  • 4 Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6845, Australia; School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia
  • 5 Department of Surgery, Taylor's University School of Medicine, Selangor, Malaysia
  • 6 School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6845, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Sir James McCusker Alzheimer's disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia
  • 7 Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6845, Australia
Int J Biochem Cell Biol, 2016 06;75:104-11.
PMID: 27063405 DOI: 10.1016/j.biocel.2016.04.002

Abstract

The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated. A wide acting family of Wnt mediators, secreted frizzled-related proteins (sFRPs), has not been probed so far as molecular indicators of disease occurrence and progression of Alzheimer's. Unlike the effect of the Dickkopf (DKK) family of Wnt antagonists on AD, the sFRP molecules have a more pleiotropic impact on the Wnt signaling cascade and probably have a far-reaching involvement in neurodegeneration. The role of sFRPs has been poorly described in AD, and in this review, we analyze the present status of the role of sFRPs on neurodegeneration, their likely involvement, and potential implications in treatment modalities of AD. This information would provide valuable clues for the development of potential therapeutic targets for aberrant neurodegenerative disorders.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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