Interactions Between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma on Neuroinflammation, Demyelination, and Remyelination in Multiple Sclerosis.
Alexandre ValléeJean-Noël ValléeRémy GuillevinYves LecarpentierPublished in: Cellular and molecular neurobiology (2017)
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.
Keyphrases
- cell proliferation
- multiple sclerosis
- stem cells
- signaling pathway
- lps induced
- immune response
- pi k akt
- traumatic brain injury
- mass spectrometry
- induced apoptosis
- insulin resistance
- oxidative stress
- ms ms
- fatty acid
- type diabetes
- poor prognosis
- metabolic syndrome
- inflammatory response
- skeletal muscle
- brain injury
- long non coding rna
- subarachnoid hemorrhage
- cell cycle arrest