| MYRF | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | MYRF , C11orf9, MRF, Ndt80, pqn-47, myelin regulatory factor, 11orf9, MMERV, CUGS | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 608329 MGI: 2684944 HomoloGene: 32167 GeneCards: MYRF | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Myelin regulatory factor | |
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| Identifiers | |
| Symbol | MYRF |
| InterPro | IPR026933 |
| Membranome | 237 |
Myelin regulatory factor (MyRF), also known as myelin gene regulatory factor (MRF), is a protein that in humans is encoded by the MYRF gene.
Myelin regulatory factor is encoded by the Myrf/GM98 gene in mice and by the MYRF gene in humans. [5] The family of MyRF-like-proteins also contains the orthologues pqn-47 from C. elegans and MYRFA from Dictyostelium . [6] All orthologs have a DNA-binding domain of high homology to the Saccharomyces cerevisiae protein Ndt80 (a p53-like transcription factor) and therefore likely act as a transcription factor.
MyRF is a transcription factor that promotes the expression of many genes important in the production of myelin. [7] It is therefore of critical importance in the development and maintenance of myelin sheaths. [8]
The expression of MYRF is specific to mature, myelinating oligodendrocytes in the CNS. [9] [10] It has been shown to be critical for the maintenance of myelin by these cells. Following ablation of MYRF the expression of myelin genes such as PLP1, MBP, MAG and MOG drops rapidly. [8] Therefore, MYRF is a key regulator and likely a direct activator of the expression of these genes. [7]
Mice that lose MYRF during adulthood present with a severe demyelination similar to that seen in animal models of multiple sclerosis. This underlines the importance of an active renewal of proteins in the myelin sheath. Further, the activity of MYRF increases during remyelination, suggesting it has a critical role in this process. [8] Animals with repressed Myrf in a proportion of oligodendrocyte precursor cells showed a delayed functional recovery from spinal cord injury. [11]
Myrf has been shown to be significantly downregulated in a mouse model carrying the same mutation in the NPC1 protein that is underlying Niemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. Therefore, a disruption of oligodendrocyte formation and myelination may be the root cause of the neurological abnormalities. [12]
Myelin is a lipid-rich extramembranous structure found on the axons and dendrites of neuron in many bilaterian animals, mainly vertebrates, as well as some arthropods and annelids. A circumferential wrapping of myelin, known as a myelin sheath, increases the conduction speed of electrical impulses passing along the axon by generating saltatory conductions, which are much faster than conduction along an unmyelinated axon, and also reduce signal loss due to extrinsic disturbances.
Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle. The two types of Schwann cells are myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue-specific manner.
Oligodendrocytes, also known as oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons within the central nervous system (CNS) of jawed vertebrates. Their function is similar to that of Schwann cells, which perform the same task in the peripheral nervous system (PNS). Oligodendrocytes accomplish this by forming the myelin sheath around axons. Unlike Schwann cells, a single oligodendrocyte can extend its processes to cover around 50 axons, with each axon being wrapped in approximately 1 μm of myelin sheath. Furthermore, an oligodendrocyte can provide myelin segments for multiple adjacent axons.
Niemann–Pick disease (NP), also known as acid sphingomyelinase deficiency, is a group of rare genetic diseases of varying severity. These are inherited metabolic disorders in which sphingomyelin accumulates in lysosomes in cells of many organs. NP types A, A/B, and B are cause by mutations in the SMPD1 gene, which causes a deficiency of a acid sphingomyelinase (ASM). NP type C is now considered a separate disease, as SMPD1 is not involved, and there is no deficiency in ASM.
Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. It is speculated to serve as a necessary "adhesion molecule" to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.
Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the CNS. This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS. The process creates a thinner myelin sheath than normal, but it helps to protect the axon from further damage, from overall degeneration, and proves to increase conductance once again. The processes underlying remyelination are under investigation in the hope of finding treatments for demyelinating diseases, such as multiple sclerosis.
Myelin-associated glycoprotein is a type 1 transmembrane protein glycoprotein localized in periaxonal Schwann cell and oligodendrocyte membranes, where it plays a role in glial-axonal interactions. MAG is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO-66 receptor, NgR. MAG is believed to be involved in myelination during nerve regeneration in the PNS and is vital for the long-term survival of the myelinated axons following myelinogenesis. In the CNS MAG is one of three main myelin-associated inhibitors of axonal regeneration after injury, making it an important protein for future research on neurogenesis in the CNS.
Niemann-Pick disease, type C1 (NPC1) is a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the NPC1 gene.
Myelinogenesis is the formation and development of myelin sheaths in the nervous system, typically initiated in late prenatal neurodevelopment and continuing throughout postnatal development. Myelinogenesis continues throughout the lifespan to support learning and memory via neural circuit plasticity as well as remyelination following injury. Successful myelination of axons increases action potential speed by enabling saltatory conduction, which is essential for timely signal conduction between spatially separate brain regions, as well as provides metabolic support to neurons.
Probable G-protein coupled receptor 37 is a protein that in humans is encoded by the GPR37 gene. GPR37 is primarily found in the central nervous system (CNS), with significant expression observed in various CNS regions including the amygdala, basal ganglia, substantia nigra, hippocampus, frontal cortex, and hypothalamus, particularly noteworthy is its exceptionally elevated expression in the spinal cord.
MHC class II regulatory factor RFX1 is a protein that, in humans, is encoded by the RFX1 gene located on the short arm of chromosome 19.
Claudin-11 is a protein that in humans is encoded by the CLDN11 gene. It belongs to the group of claudins and was the first member of the family to be knocked out in mice, thereby demonstrating the central role of claudins for intramembranous strands observed in freeze-fracture images.
Oligodendrocyte transcription factor 1 is a protein that in humans is encoded by the OLIG1 gene.
Myelin transcription factor 1 is a protein that in humans is encoded by the MYT1 gene.
Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo receptor also known as the reticulon 4 receptor.
2′,3′-Cyclic-nucleotide 3'-phosphodiesterase is an enzyme that in humans is encoded by the CNP gene.
Homeobox protein Nkx-6.2 is a protein that in humans is encoded by the NKX6-2 gene.
Gap junction gamma-3, also known as connexin-29 (Cx29) or gap junction epsilon-1 (GJE1), is a protein that in humans is encoded by the GJC3 gene.
Patrizia Casaccia is an Italian neuroscientist who is the Director of the Neuroscience Initiative of the Advanced Science Research Center at the City University of New York (CUNY), as well as a Professor of Neuroscience, Genetics & Genomics, and Neurology at the Icahn School of Medicine at Mount Sinai. Casaccia is a pioneer in the study of myelin. Her research focuses on understanding the neurobiological and neuroimmune mechanisms of multiple sclerosis and to translate findings into treatments. Casaccia co-founded the Center for Glial Biology at Mount Sinai and CUNY and is one of the Directors of the center.
Myelinoids or myelin organoids are three dimensional in vitro cultured model derived from human pluripotent stem cells (hPSCs) that represent various brain regions, spinal cord or the peripheral nervous system in early fetal human development. They have the capacity to recapitulate aspects of brain developmental processes, microenvironments, cell to cell interaction, structural organization and cellular composition. The differentiating aspect dictating whether an organoid is deemed a cerebral organoid/brain organoid or myelinoid is the presence of myelination and compact myelin formation that is a defining feature of myelinoids. Due to the complex nature of the human brain, there is a need for model systems which can closely mimic complicated biological processes. Myelinoids provide a unique in vitro model through which myelin pathology, neurodegenerative diseases, developmental processes and therapeutic screening can be accomplished.
