MANF: A New Player in the Control of Energy Homeostasis, and Beyond

All human behaviors, including the control of energy homeostasis, are ultimately mediated by neuronal activities in the brain. Neurotrophic factors represent a protein family that plays important roles in regulating neuronal development, function, and survival. It has been well established that canonical neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), play important roles in the central regulation of energy homeostasis. Recently, a class of non-canonical neurotrophic factors, represented by mesencephalic astrocyte-derived neurotrophic factor (MANF), has been discovered. MANF is structurally and functionally distinct from those canonical neurotrophic factors, hence raising the issue of MANF being non-canonical. Nonetheless, emerging evidence suggests that MANF is critically involved in many neuronal activities. Here, we review our current understanding about the functions of MANF in the brain, with a primary focus on the control of energy homeostasis.