The role of <it>Wnt </it>signaling in neuronal dysfunction in Alzheimer's Disease

• Main Authors: Toledo Enrique M, Inestrosa Nibaldo C
• Format: Article
• Language: English
• Published: BMC 2008-07-01
• Series: Molecular Neurodegeneration
• Online Access: http://www.molecularneurodegeneration.com/content/3/1/9

<p>Abstract</p> <p>Recent evidence supports a neuroprotective role for <it>Wnt </it>signaling in neurodegenerative disorders such as Alzheimer's Disease (AD). In fact, a relationship between amyloid-β-peptide (Aβ)-induced neurotoxicity and a decrease in the cytoplasmic levels of β-catenin has been observed. Apparently Aβ binds to the extracellular cysteine-rich domain of the Frizzled receptor (Fz) inhibiting <it>Wnt</it>/β-catenin signaling. Cross-talk with other signaling cascades that regulate <it>Wnt</it>/β-catenin signaling, including the activation of M₁muscarinic receptor and PKC, the use of Ibuprofen-ChE bi-functional compounds, PPAR α, γ agonists, nicotine and some antioxidants, results in neuroprotection against Aβ. These studies indicate that a sustained loss of <it>Wnt </it>signaling function may be involved in the Aβ-dependent neurodegeneration observed in Alzheimer's brain. In conclusion the activation of the <it>Wnt </it>signaling pathway could be proposed as a therapeutic target for the treatment of AD.</p>