Abstract
Adropin is a 4.9 kDa peptide that is important for maintenance of metabolic and non-metabolic homeostasis. It regulates glucose and fatty acid metabolism and is involved in endothelial cell function and endothelial nitric oxide (NO) synthase bioactivity as well as physical activity and motor coordination. Adropin is expressed in many tissues and organs including central nervous system (CNS). This peptide plays a crucial role in the development of various CNS disorders such as stroke, schizophrenia, bipolar disorder as well as Alzheimer's, Parkinson's, and Huntington's diseases. In this comprehensive review, the potential roles of adropin in cellular signaling pathways that lead to pathogenesis and/or treatment of CNS disorders will be discussed.
Highlights
Adropin is a 4.9 kDa peptide encoded by Energy Homeostasis Associated gene (Enho) located on chromosome 9 (Kumar et al, 2008; Aydin, 2014)
Adropin suppresses two key enzymes in fatty acid utilization: carnitine palmitoyltransferase-1B (CPT-1B) and Cluster of Differentiation 36 (CD36) (Gao et al, 2015); it plays a role in fatty acid oxidation
Variation in AKT1—one of the three genes encoding Akt—has been associated with schizophrenia and bipolar disorders (Ikeda et al, 2004; Karege et al, 2012), PI3K/Akt activation by adropin might have a therapeutic potential in disorders such as Parkinson’s (Burke, 2007; Timmons et al, 2009) and schizophrenia (Schwab et al, 2005) as discussed below: Ischemic Insult Cerebral ischemic injuries cause neural loss secondary to apoptosis or necrosis—which can be triggered by oxidative stress, metabolic compromise and disruption of calcium homeostasis at the cellular level (Mattson et al, 2001)
Summary
Adropin is a 4.9 kDa peptide encoded by Energy Homeostasis Associated gene (Enho) located on chromosome 9 (Kumar et al, 2008; Aydin, 2014). Adropin’s function as a regulator of glucose and lipid homeostasis and insulin sensitivity was initially described in 2008 by Kumar et al (2008) and later by Aydin (2014). Lovren et al (2010) demonstrated the endothelial protective potentials of adropin in 2010. Adropin activates vascular endothelial growth factor receptor 2 (VEGFR2) and its two downstream signaling pathways—phosphatidylinositol-3 kinase/ serine, threonine kinase (PI3K/Akt) and extracellular signal-regulated kinases 1/2 (ERK 1/2) (Figure 1). Adropin modulates expression of endothelial nitric oxide synthase (eNOS) (Lovren et al, 2010). Adropin enhances mitochondrial function and activates pyruvate dehydrogenase (PDH)—a rate-limiting enzyme in glucose oxidation. Adropin suppresses two key enzymes in fatty acid utilization: carnitine palmitoyltransferase-1B (CPT-1B) and Cluster of Differentiation 36 (CD36) (Gao et al, 2015); it plays a role in fatty acid oxidation
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