Neuregulins are a family of four structurally related proteins that are part of the EGF family of proteins. These proteins have been shown to have diverse functions in the development of the nervous system and play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses.
Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ERBB2 gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently referred to as HER2 or CD340.
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.
Neuregulin 1, or NRG1, is a gene of the epidermal growth factor family that in humans is encoded by the NRG1 gene. NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. Neuregulin 1 is produced in numerous isoforms by alternative splicing, which allows it to perform a wide variety of functions. It is essential for the normal development of the nervous system and the heart.
The nuclear receptor 4A2 (NR4A2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the NR4A2 gene. NR4A2 is a member of the nuclear receptor family of intracellular transcription factors.
Rev-Erb alpha (Rev-Erbɑ), also known as nuclear receptor subfamily 1 group D member 1 (NR1D1), is one of two Rev-Erb proteins in the nuclear receptor (NR) family of intracellular transcription factors. In humans, REV-ERBɑ is encoded by the NR1D1 gene, which is highly conserved across animal species.
Rev-Erb beta (Rev-Erbβ), also known as nuclear receptor subfamily 1 group D member 2 (NR1D2), is a member of the Rev-Erb protein family. Rev-Erbβ, like Rev-Erbα, belongs to the nuclear receptor superfamily of transcription factors and can modulate gene expression through binding to gene promoters. Together with Rev-Erbα, Rev-Erbβ functions as a major regulator of the circadian clock. These two proteins are partially redundant. Current research suggests that Rev-Erbβ is less important in maintaining the circadian clock than Rev-Erbα; knock-out studies of Rev-Erbα result in significant circadian disruption but the same has not been found with Rev-Erbβ. Rev-Erbβ compensation for Rev-Erbα varies across tissues, and further research is needed to elucidate the separate role of Rev-Erbβ.
Receptor tyrosine-protein kinase erbB-3, also known as HER3, is a membrane bound protein that in humans is encoded by the ERBB3 gene.
Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.
Kalirin, also known as Huntingtin-associated protein-interacting protein (HAPIP), protein duo (DUO), or serine/threonine-protein kinase with Dbl- and pleckstrin homology domain, is a protein that in humans is encoded by the KALRN gene. Kalirin was first identified in 1997 as a protein interacting with huntingtin-associated protein 1. Is also known to play an important role in nerve growth and axonal development.
The GABAA beta-2 subunit is a protein that in humans is encoded by the GABRB2 gene. It combines with other subunits to form the ionotropic GABAA receptors. GABA system is the major inhibitory system in the brain, and its dominant GABAA receptor subtype is composed of α1, β2, and γ2 subunits with the stoichiometry of 2:2:1, which accounts for 43% of all GABAA receptors. Alternative splicing of the GABRB2 gene leads at least to four isoforms, viz. β2-long (β2L) and β2-short. Alternatively spliced variants displayed similar but non-identical electrophysiological properties. GABRB2 is subjected to positive selection and known to be both an alternative splicing and a recombination hotspot; it is regulated via epigenetic regulation including imprinting and gene and promoter methylation GABRB2 has been associated with a number of neuropsychiatric disorders, and found to display altered expression in cancer.
Protein phosphatase 1 regulatory subunit 1B (PPP1R1B), also known as dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32), is a protein that in humans is encoded by the PPP1R1B gene.
SH3 and multiple ankyrin repeat domains protein 2 is a protein that in humans is encoded by the SHANK2 gene. Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full-length nature has not been determined.
ERBB receptor feedback inhibitor 1 is a protein that in humans is encoded by the ERRFI1 gene.
Neuregulin 2, also known as NRG2, is a protein which in humans is encoded by the NRG2 gene.
The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms of schizophrenia linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors. While thought to be more proximal to the root causes of schizophrenia, it does not negate the dopamine hypothesis, and the two may be ultimately brought together by circuit-based models. The development of the hypothesis allowed for the integration of the GABAergic and oscillatory abnormalities into the converging disease model and made it possible to discover the causes of some disruptions.
Neuregulin 4 also known as NRG4 is a member of the neuregulin protein family which in humans is encoded by the NRG4 gene.
Research into the mental disorder of schizophrenia, involves multiple animal models as a tool, including in the preclinical stage of drug development.
Behavioral epigenetics is the field of study examining the role of epigenetics in shaping animal and human behavior. It seeks to explain how nurture shapes nature, where nature refers to biological heredity and nurture refers to virtually everything that occurs during the life-span. Behavioral epigenetics attempts to provide a framework for understanding how the expression of genes is influenced by experiences and the environment to produce individual differences in behaviour, cognition, personality, and mental health.
Epigenetics of bipolar disorder is the effect that epigenetics has on triggering and maintaining bipolar disorder.
