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

Sudha Warrier, Raja Marimuthu, Sreeja Sekhar, G. Bhuvanalakshmi, Frank Arfuso, Anjan Kumar Das, Ramesh Bhonde, Ralph Martins, Arun Dharmarajan

Research output: Contribution to journalReview article

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume75
DOIs
Publication statusPublished - 01-06-2016

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Alzheimer Disease
Neurodegenerative Diseases
Wnt Receptors
Catenins
Therapeutics
Amyloid
Disease Progression
Biomarkers
Ligands
Peptides
FRZB protein
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

Warrier, Sudha ; Marimuthu, Raja ; Sekhar, Sreeja ; Bhuvanalakshmi, G. ; Arfuso, Frank ; Das, Anjan Kumar ; Bhonde, Ramesh ; Martins, Ralph ; Dharmarajan, Arun. / SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease. In: International Journal of Biochemistry and Cell Biology. 2016 ; Vol. 75. pp. 104-111.
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Warrier, S, Marimuthu, R, Sekhar, S, Bhuvanalakshmi, G, Arfuso, F, Das, AK, Bhonde, R, Martins, R & Dharmarajan, A 2016, 'SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease', International Journal of Biochemistry and Cell Biology, vol. 75, pp. 104-111. https://doi.org/10.1016/j.biocel.2016.04.002

SFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease. / Warrier, Sudha; Marimuthu, Raja; Sekhar, Sreeja; Bhuvanalakshmi, G.; Arfuso, Frank; Das, Anjan Kumar; Bhonde, Ramesh; Martins, Ralph; Dharmarajan, Arun.

In: International Journal of Biochemistry and Cell Biology, Vol. 75, 01.06.2016, p. 104-111.

Research output: Contribution to journalReview article

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AU - Warrier, Sudha

AU - Marimuthu, Raja

AU - Sekhar, Sreeja

AU - Bhuvanalakshmi, G.

AU - Arfuso, Frank

AU - Das, Anjan Kumar

AU - Bhonde, Ramesh

AU - Martins, Ralph

AU - Dharmarajan, Arun

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

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