Neudesin as a unique secreted protein with multi-functional roles in neural functions, energy metabolism, and tumorigenesis

Abstract

Neudesin was originally identified as a secreted protein with neurotrophic activity, and, thereafter, was also termed neuron-derived neurotrophic factor (NENF) or the candidate oncogene GIG47. Neudesin with a conserved cytochrome 5-like heme/steroid-binding domain activates intracellular signaling pathways possibly through the activation of G protein-coupled receptors. In the brain, hypothalamic Neudesin decreases food intake. Neudesin knockout (KO) mice also exhibit anxiety-like behavior, indicating its roles in the hippocampal anxiety circuitry. Neudesin is also expressed in various peripheral tissues. Neudesin KO mice are strongly resistant to high-fat diet (HFD)-induced obesity due to elevated systemic sympathetic activity, heat production, and adipocytic lipolysis. Neudesin, which is over-expressed or induced by DNA hypomethylation in multiple human cancers, also stimulates tumorigenesis. These findings indicate that Neudesin plays roles in neural functions, energy metabolism, and tumorigenesis and is expected to be a novel target for obesity and anti-cancer treatments.

Membrane Associated Progesterone Receptors: Promiscuous Proteins with Pleiotropic Functions – Focus on Interactions with Cytochromes P450

“…The physiological roles of neudesin as a secreted protein appear to be significantly different from PGRMC1/2, including particularly neurotrophic activity that required heme binding and was mediated through mitogen-activated protein (MAP) and phosphatidylinositol 3-kinase (PI-3K) pathways (Kimura et al, 2005). Several neurological functions have been studied in knockout mice as summarized elsewhere (Ohta et al, 2015). Extracellular/secreted neudesin may be involved in carcinogen resistance and tumor cell immortalization, although specific receptors remain unknown (Ohta et al, 2015).…”

“…Several neurological functions have been studied in knockout mice as summarized elsewhere (Ohta et al, 2015). Extracellular/secreted neudesin may be involved in carcinogen resistance and tumor cell immortalization, although specific receptors remain unknown (Ohta et al, 2015). …”

<p>Neudesin in obesity and type 2 diabetes mellitus: the effect of acute fasting and weight reducing interventions</p>

“…Neudesin is a newly identified factor contributing to the complex control of energy homeostasis 8. It was originally identified in mice embryos as a secreted protein with neurotrophic activity 9.…”

The evolutionary appearance of signaling motifs in PGRMC1

“…This may be because Neudesin and Neferricin are present in the luminal compartment and secreted extracellularly (2,3,(24)(25)(26)(27)(28), however the presence of some observed phosphorylation events suggests that the MAPR domain of these proteins may also be found in the cytoplasm. The detection of O-N-acetylgalactosamine (O-GalNAc) glycosylation does not necessarily imply an extracellular location for Neudesin, since 14% of O-GalNAc proteins are annotated with nuclear Gene Ontogeny (GO) assignments (29).…”