FGF21 Promotes Remyelination in the Central Nervous System

In this study, we found that circulating FGF21 promotes OPC proliferation. OPC proliferation was elevated in the spinal cords of mice with toxin-induced demyelination, and this proliferation was inhibited by silencing of FGF21 expression in the pancreas. OPCs expressed β-klotho, an essential coreceptor for FGF21, and inhibition of β-klotho expression in OPCs prevented the increase in OPC proliferation and subsequent remyelination. The results of this study reveal an unexpected role of FGF21, which has been previously characterized as a metabolic regulator. In reviewing previous findings regarding FGF21 function in the CNS, we noted that FGF21 can cross the blood-brain barrier, but the FGF21 level in the cerebrospinal fluid of healthy patients is approximately 40% of that in the plasma. Thus, CNS entry of peripheral FGF21 is limited in normal adult subjects. We should note that FGF21-mediated OPC proliferation is only one of the mechanisms of remyelination. In terms of molecular mechanism, we just focused on the direct action of FGF21 on OPC proliferation; however, FGF also regulates expression of VEGF receptor 2. Because VEGF signaling is related to brain homeostasis, including OPC migration, a process that involves remyelination, an indirect effect of FGF21 on OPCs may also contribute to oligodendrocyte development and remyelination. Meanwhile, FGF21-associated drugs for treating diabetes have recently been developed by pharmaceutical companies, and some of these c...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs