Molecular Insights to the Wnt Signaling During Alzheimer’s Disorder: a Potential Target for Therapeutic Interventions
- 7 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Molecular Neuroscience
- Vol. 72 (4), 679-690
- https://doi.org/10.1007/s12031-021-01940-5
Abstract
In the adult brain, Wnt signaling is crucial for neurogenesis, and it also regulates neuronal development, neuronal maturation, neuronal differential, and proliferation. Impaired Wnt signaling pathways are associated with enhanced levels of amyloid-β, reduced β-catenin levels, and increased expression of GSK-3β enzyme, suggesting its direct association with the pathogenesis of Alzheimer’s disorder (AD). These findings are consolidated by reports where activation of Wnt signaling by genetic factors and pharmacological intervention has improved the cognitive functions in animals and restored neurogenesis in the adult brain. Various natural and synthetic molecules have been identified that modulate Wnt signaling in the adult brain and promote neurogenesis and alleviate behavioral dysfunction. These molecules include lithium, valproic acid, ethosuximide, selenomethionine, curcumin, andrographolide, xanthoceraside, huperzine A, pyridostigmine, ginkgolide-B, ricinine, cannabidiol, and resveratrol. These molecules are associated with the DKK1 and GSK-3β inhibition and β-catenin stabilization along with their effects on neurogenesis, neuronal proliferation, and differentiation in the hippocampus through modulation of Wnt signaling and thereby could prove beneficial in the management of AD pathogenesis. Although modulation of the Wnt signaling seems to suggest to be promising in the management of AD, unfortunately, most of the literature available for the association of Wnt signaling and AD pathogenesis is either from preclinical studies or post-mortem brain. Therefore, it will be interesting to understand the role of Wnt signaling in AD patients, and a rigorous investigation could provide us with a better understanding of AD pathogenesis and the identification of novel targets for therapeutic interventions.This publication has 120 references indexed in Scilit:
- Biochemistry and Cell Biology of Tau Protein in Neurofibrillary DegenerationCold Spring Harbor Perspectives in Medicine, 2012
- Wnt7a signaling promotes dendritic spine growth and synaptic strength through Ca 2+ /Calmodulin-dependent protein kinase IIProceedings of the National Academy of Sciences of the United States of America, 2011
- Huperzine A Activates Wnt/β-Catenin Signaling and Enhances the Nonamyloidogenic Pathway in an Alzheimer Transgenic Mouse ModelNeuropsychopharmacology, 2011
- Lithium Improves Hippocampal Neurogenesis, Neuropathology and Cognitive Functions in APP Mutant MicePLOS ONE, 2010
- Wnt signaling in development and diseaseNeurobiology of Disease, 2010
- Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNSGenes & Development, 2009
- Wnts acting through canonical and noncanonical signaling pathways exert opposite effects on hippocampal synapse formationNeural Development, 2008
- Wnt/β-catenin signaling controls development of the blood–brain barrierThe Journal of cell biology, 2008
- The GSK3 hypothesis of Alzheimer’s diseaseJournal of Neurochemistry, 2007
- Tau phosphorylation by GSK-3β promotes tangle-like filament morphologyMolecular Neurodegeneration, 2007