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Sep 24, 2018

Known Drug Might Prove Effective Against Alzheimer’s Disease

Posted by in categories: biotech/medical, neuroscience

Apparently, amyloid beta drives its own production in a vicious circle.


In a study at King’s College London, scientists have shown that a vicious circle in which the ill-famed amyloid-beta protein stimulates its own production might be a key factor in the etiology of neurodegeneration in Alzheimer’s disease; furthermore, a drug known as fasudil seems to be effective against amyloid-beta in a mice model of the disease [1].

Study abstract

In Alzheimer’s disease (AD), the canonical Wnt inhibitor Dickkopf-1 (Dkk1) is induced by β-amyloid (Aβ) and shifts the balance from canonical towards non-canonical Wnt signalling. Canonical (Wnt-β-catenin) signalling promotes synapse stability, while non-canonical (Wnt-PCP) signalling favours synapse retraction; thus Aβ-driven synapse loss is mediated by Dkk1. Here we show that the Amyloid Precursor Protein (APP) co-activates both arms of Wnt signalling through physical interactions with Wnt co-receptors LRP6 and Vangl2, to bi-directionally modulate synapse stability. Furthermore, activation of non-canonical Wnt signalling enhances Aβ production, while activation of canonical signalling suppresses Aβ production. Together, these findings identify a pathogenic-positive feedback loop in which Aβ induces Dkk1 expression, thereby activating non-canonical Wnt signalling to promote synapse loss and drive further Aβ production.

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