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

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, ß-catenin, has been linked to...

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Main Authors: Warrier, Sudha, Marimuthu, R., Sekhar, S., Bhuvanalakshmi, G., Arfuso, Frank, Das, A., Bhonde, R., Martins, R., Dharmarajan, Arunasalam
Format: Journal Article
Published: Pergamon 2016
Online Access:http://hdl.handle.net/20.500.11937/30058
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author Warrier, Sudha
Marimuthu, R.
Sekhar, S.
Bhuvanalakshmi, G.
Arfuso, Frank
Das, A.
Bhonde, R.
Martins, R.
Dharmarajan, Arunasalam
author_facet Warrier, Sudha
Marimuthu, R.
Sekhar, S.
Bhuvanalakshmi, G.
Arfuso, Frank
Das, A.
Bhonde, R.
Martins, R.
Dharmarajan, Arunasalam
author_sort Warrier, Sudha
building Curtin Institutional Repository
collection Online Access
description 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, ß-catenin, has been linked to amyloid-ß-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.
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spelling curtin-20.500.11937-300582017-09-13T15:37:43Z SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease Warrier, Sudha Marimuthu, R. Sekhar, S. Bhuvanalakshmi, G. Arfuso, Frank Das, A. Bhonde, R. Martins, R. Dharmarajan, Arunasalam 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, ß-catenin, has been linked to amyloid-ß-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. 2016 Journal Article http://hdl.handle.net/20.500.11937/30058 10.1016/j.biocel.2016.04.002 Pergamon fulltext
spellingShingle Warrier, Sudha
Marimuthu, R.
Sekhar, S.
Bhuvanalakshmi, G.
Arfuso, Frank
Das, A.
Bhonde, R.
Martins, R.
Dharmarajan, Arunasalam
SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
title SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
title_full SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
title_fullStr SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
title_full_unstemmed SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
title_short SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
title_sort sfrp-mediated wnt sequestration as a potential therapeutic target for alzheimer's disease
url http://hdl.handle.net/20.500.11937/30058