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Wnt
signaling is important for neuronal
function and survival and accumulating
evidence points to inhibition of Wnt
signaling as a likely component of neurodegeneration
associated with Alzheimer’s disease
(AD).
The protein DKK1 is a secreted inhibitor
of the canonical Wnt signaling pathway
whose expression is increased by the
amyloid-b (Ab) peptide in neuronal cultures
and in patients suffering from AD (Caricasole
et al., 2004). Induction of DKK1 expression
is also a component of neurotoxicity
associated with ischemic neuronal damage
(Cappuccio et al., 2005).
Small molecule antagonists of DKK1 should
protect against the neurotoxicity induced
by inhibition of Wnt signaling and may
therefore form the basis for a novel
therapeutic approach for the treatment
of AD. |
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