Neuropeptide Y (NPY), a 36-amino acid peptide, is widely distributed in the central and peripheral nervous systems and other peripheral tissues. poor survival and low differentiation and integration rates of transplanted stem cells. The regulatory effects of NPY on stem cell survival, proliferation, and differentiation may be helpful to overcome these limitations and facilitate the application of stem cell-based therapy. In this review, we summarized the regulatory effects of NPY on stem cells and discussed their potential applications in disease therapy. 1. Introduction NPY, a 36-amino acid neuropeptide, was first isolated by Tatemoto et al. from swine brain in 1982 ; it belongs to the pancreatic polypeptide family together with pancreatic polypeptide (PP) and peptide YY (PYY). NPY, whose structure is characterized by a large number of tyrosine residues (5 of 36 amino acid residues) and an amidated C-terminal group, remained highly conserved among species in the course of evolution . As one of the most abundant neuropeptides, NPY is widely present in the central and peripheral nervous systems (CNS/PNS) and is a crucial mediator for other peripheral tissues. In the CNS, it is distributed in regions such as the cerebral cortex, hypothalamus, brainstem, hippocampus, striatum, and limbic structures [2C4]. In the PNS, MLN8237 it is expressed in sympathetic ganglia and costored and coreleased with noradrenaline during sympathetic nerve stimulation . Mounting evidence indicates that NPY expresses in many peripheral tissues such as the retina, MLN8237 bone, adipose tissue, adrenal medulla, and platelets [6C10]. Consistent with its wide distribution, NPY has been implicated in a variety of biological processes including food intake, circadian rhythm, energy metabolism, cardiovascular function, and neuroendocrine secretion [11C15]. Five NPY receptors (Y1, Y2, Y4, Y5, and y6) have been identified in mammals, which all belong to the super family of G protein-coupled receptors. However, the Y4 receptor has limited affinity for NPY . The y6 receptor is not functional in primates as their y6 gene exists in a truncated version missing the seventh transmembrane domain [17, 18]. NPY receptors are also widely distributed in central and peripheral tissues of which each receptor exhibits different distributions and mediates their MLN8237 specific functions . Stem cells are a kind of primitive and undifferentiated cells which are characterized by perpetual self-renewal and the potency to differentiate into Rabbit Polyclonal to CDK1/CDC2 (phospho-Thr14) specialized cell types. Based on their origin, stem cells can be categorized into two MLN8237 types: embryonic stem cells (ESCs) and non-ESCs . The non-ESCs are derived from adult and fetal tissues including hematopoietic stem cells, bone marrow mesenchymal stem cells, adipose-derived stem cells, neural stem cells, and dental pulp stem cells . Stem cells have the therapeutic potential to replace damaged cells, secrete paracrine molecules, promote angiogenesis, modulate immunity, and facilitate tissue repair [22, 23]. Hence, the efficacy of stem cell-based therapy has been described in many diseases including myocardial infarction, stroke, neuritis, liver cirrhosis, pulmonary fibrosis, spinal cord injuries (SCI), Parkinson’s disease, and Alzheimer’s disease [24C31]. However, some limitations still hamper the application of stem cell-based therapy, such as poor survival, oncogenic potential, and low differentiation and integration rates, which need to be further researched to open up new avenues for the therapy. 2. Effects of NPY on Stem Cells Increasing researches indicate that NPY exerts regulatory effects on the proliferation, differentiation, and survival of stem cells, which is speculated to have potential applications in treatment for many diseases. Here, we reviewed the effects of NPY on different stem cells and the involved mechanisms (Figure 1). Figure 1 Main effects of NPY on different stem cells. NPY exerts multiple regulatory effects on MSC functions, including proliferation (via Y5R), differentiation (via Y2R and Y1R), migration, tube formation, and expression of VEGF and CXCR4. NPY could promote … 2.1. NPY and Neural Stem/Precursor Cells (NSPCs) 2.1.1. Hippocampal Precursor Cells Howell et al. uncovered that NPY increased the neurosphere formation of early postnatal rat-derived primary hippocampal cultures as well as the 5-bromo-2-deoxyuridine (BrdU) incorporation of nestin+ hippocampal precursor cells, MLN8237 which indicated that NPY could promote the proliferation of hippocampal precursor cells. Besides using NPY receptor agonists.