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Environmental factors such as heavy metal toxicity [1012], sub-clinical viral infections [13] and gastro-intestinal pathology [14, 15], as well as endogenous toxins produced by metabolic processes [16], hormones (reviewed in [17]) and gastro-intestinal bacteria [18, 19] have also been suggested as playing a role in the aetiology of the disorder, although none of these have been thoroughly investigated

In canonical Wnt/-catenin signaling, the secreted Wnt ligands bind with the Frizzled receptor, which further inactivates glycogen synthase kinase-3 (GSK-3), which is an enzyme responsible for the ubiquitination-mediated degradation of -catenin 4,5

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