title: sFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease.
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.
authors.affiliation: 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.
authors.forename: Sudha
authors.initials: S
authors.lastname: Warrier
authors.affiliation: Department of Orthopedics, Sree Balaji Medical College and Hospital, Chromepet, Chennai 600044, India.
authors.forename: Raja
authors.initials: R
authors.lastname: Marimuthu
authors.affiliation: Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 065, India.
authors.forename: Sreeja
authors.initials: S
authors.lastname: Sekhar
authors.affiliation: Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 065, India.
authors.forename: G
authors.initials: G
authors.lastname: Bhuvanalakshmi
authors.affiliation: 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.
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.affiliation: Department of Surgery, Taylor's University School of Medicine, Selangor, Malaysia.
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Das
authors.affiliation: Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 065, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhonde
authors.affiliation: 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.
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.affiliation: Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6845, Australia.
authors.forename: Arun
authors.initials: A
authors.lastname: Dharmarajan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D018450:Disease Progression; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D058990:Molecular Targeted Therapy / Q000379:methods*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins
keywords: Alzheimer’s disease; Neurodegeneration; Wnt; sFRP