Wnt Signaling And Multiple Sclerosis

By Quasar Jarosz at English Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7616130

The paper linked here asserts that downregulation of Wnt signaling (also involved in many types of cancer) is essential for proper neuronal differentiation, and that activated Wnt signaling can impair remyelination of neurons. Since demyelination – loss of the myelin sheath of neurons that is important for nerve signal conduction – leads to multiple sclerosis, this finding points the way for possible therapeutic interventions against that disease.  Abstract:

Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation. The activation of WNT/beta-catenin pathway results in differentiation failure and impairment in remyelination. However, PI3K/Akt pathway and TCF7L2, two downstream targets of WNT/beta-catenin pathway, are upregulated and promote proper remyelination. The interactions of these signaling pathways remain unclear. PPAR gamma activation can inhibit NF-kappaB, and can also downregulate the WNT/beta-catenin pathway. PPAR gamma and canonical WNT/beta-catenin pathway act in an opposite manner. PPAR gamma agonists appear as a promising treatment for the inhibition of demyelination and the promotion of proper remyelination through the control of both NF-kappaB activity and canonical WNT/beta-catenin pathway.