Dimethylarginine dimethylaminohydrolase 1 as a novel regulator of oligodendrocyte differentiation in the central nervous system remyelination

Glia ◽  
2021 ◽  
Author(s):  
Akiko Uyeda ◽  
Lili Quan ◽  
Yuki Kato ◽  
Nagaaki Muramatsu ◽  
Shogo Tanabe ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oligodendrocyte Differentiation ◽  
Dimethylarginine Dimethylaminohydrolase ◽  
The Central Nervous System

scholarly journals Loss of PRMT5 promotes PDGFRα degradation during oligodendrocyte differentiation and myelination

2018 ◽  
Author(s):  
Sara Calabretta ◽  
Gillian Vogel ◽  
Zhenbao Yu ◽  
Karine Choquet ◽  
Lama Darbelli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Arginine Methylation ◽  
Platelet Derived Growth Factor ◽  
Oligodendrocyte Differentiation ◽  
The Central Nervous System ◽  
Cns Myelination

SummaryPlatelet derived growth factor receptor α (PDGFRα) signaling is required for proliferation, commitment and maintenance of oligodendrocyte (OL) precursor cells (OPCs). PDGFRα signaling promotes OPC homeostasis and its attenuation signals OPC differentiation and maturation triggering the onset of myelination of the central nervous system (CNS). The initial steps of how PDGFRα signaling is attenuated are still poorly understood. Herein we show that decreased Protein Arginine MethylTransferase5 (PRMT5) expression, as occurs during OPC differentiation, is involved in the down-regulation of PDGFRα by modulating its cell surface bioavailability leading to its degradation in a Cbldependent manner. Mechanistically, loss of arginine methylation at R554 of the PDGFRα intracellular domain reveals a masked Cbl binding site at Y555. Physiologically, depletion of PRMT5 in OPCs results in severe CNS myelination defects. We propose that decreased PRMT5 activity initiates PDGFRα degradation to promote OL differentiation. More broadly, inhibition of PRMT5 may be used therapeutically to manipulate PDGFRα bioavailability.

scholarly journals Notch1 control of oligodendrocyte differentiation in the spinal cord

2002 ◽  
Vol 158 (4) ◽  
pp. 709-718 ◽  
Author(s):  
Stéphane Genoud ◽  
Corinna Lappe-Siefke ◽  
Sandra Goebbels ◽  
Freddy Radtke ◽  
Michel Aguet ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Oligodendrocyte Differentiation ◽  
Temporal Regulation ◽  
Development And Differentiation ◽  
The Central Nervous System

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.

scholarly journals Divergent Dimethylarginine Dimethylaminohydrolase Isoenzyme Expression in the Central Nervous System

2021 ◽  
Author(s):  
Alena A. Kozlova ◽  
Vinitha N. Ragavan ◽  
Natalia Jarzebska ◽  
Iana V. Lukianova ◽  
Anastasia E. Bikmurzina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Regions ◽  
Nitric Oxide Synthases ◽  
Renal Diseases ◽  
Cellular Distribution ◽  
Dimethylarginine Dimethylaminohydrolase ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System

AbstractThe endogenous methylated derivative of ʟ-arginine, Nω,Nω′-dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism. A current impediment is limited knowledge on specific tissue and cellular distribution of DDAH enzymes within the brain. In this study, we provide a detailed characterization of the regional and cellular distribution of DDAH1 and DDAH2 proteins in the adult murine and human brain. Immunohistochemical analysis showed a wide distribution of DDAH1, mapping to multiple cell types, while DDAH2 was detected in a limited number of brain regions and exclusively in neurons. Our results provide key information for the investigation of the pathophysiological roles of the ADMA/DDAH system in neuropsychiatric diseases and pave the way for the development of novel selective therapeutic approaches.

scholarly journals Divergent dimethylarginine dimethylaminohydrolase isoenzyme expression in the central nervous system

2021 ◽  
Author(s):  
Alena Alekseevna Kozlova ◽  
Vinitha Nair Ragavan ◽  
Natalia Jarzebska ◽  
Iana Vadimovna Lukianova ◽  
Anastasia Evgenievna Bikmurzina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Regions ◽  
Nitric Oxide Synthases ◽  
Renal Diseases ◽  
Cellular Distribution ◽  
Dimethylarginine Dimethylaminohydrolase ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System

Abstract The endogenous methylated derivative of L-arginine, N G -N G -dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism. A current impediment is the limited data on specific tissue and cellular distribution of DDAH enzymes within the brain. In this study, we provide a detailed characterization of the regional and cellular distribution of DDAH1 and DDAH2 proteins in adult murine and human brain. Immunohistochemical analysis showed a wide distribution of DDAH1, mapping to multiple cell types, while DDAH2 was detected in a limited number of brain regions and exclusively in neurons. Our results provide key information for the investigation of the pathophysiological roles of the ADMA/DDAH system in neuropsychiatric diseases and pave the way for the development of novel selective therapeutic approaches.

scholarly journals Divergent dimethylarginine dimethylaminohydrolase isoenzyme expression in the central nervous system

2021 ◽  
Author(s):  
Alena A Kozlova ◽  
Vinitha N Ragavan ◽  
Natalia Jarzebska ◽  
Iana V Lukianova ◽  
Anastasia E Bikmurzina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Regions ◽  
Nitric Oxide Synthases ◽  
Renal Diseases ◽  
Cellular Distribution ◽  
Dimethylarginine Dimethylaminohydrolase ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System

Abstract The endogenous methylated derivative of L-arginine, NG-NG-dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism. A current impediment is the limited data on specific tissue and cellular distribution of DDAH enzymes within the brain. In this study, we provide a detailed characterization of the regional and cellular distribution of DDAH1 and DDAH2 proteins in adult murine and human brain. Immunohistochemical analysis showed a wide distribution of DDAH1, mapping to multiple cell types, while DDAH2 was detected in a limited number of brain regions and exclusively in neurons. Our results provide key information for the investigation of the pathophysiological roles of the ADMA/DDAH system in neuropsychiatric diseases and pave the way for the development of novel selective therapeutic approaches.

scholarly journals R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System

2018 ◽  
Vol 38 (22) ◽  
pp. 5096-5110 ◽  
Author(s):  
Miriam Sanz-Rodriguez ◽  
Agnès Gruart ◽  
Juan Escudero-Ramirez ◽  
Fernando de Castro ◽  
José María Delgado-García ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oligodendrocyte Differentiation ◽  
The Central Nervous System

Contactin1a expression is associated with oligodendrocyte differentiation and axonal regeneration in the central nervous system of zebrafish

2007 ◽  
Vol 35 (2) ◽  
pp. 194-207 ◽  
Author(s):  
Jörn Schweitzer ◽  
Dimitrios Gimnopoulos ◽  
Bettina C. Lieberoth ◽  
Hans-Martin Pogoda ◽  
Julia Feldner ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Oligodendrocyte Differentiation ◽  
The Central Nervous System

scholarly journals Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

2021 ◽  
Vol 15 ◽  
Author(s):  
Junko Nio-Kobayashi ◽  
Tetsuya Itabashi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Glial Cells ◽  
Expression Patterns ◽  
Neural Regeneration ◽  
Oligodendrocyte Differentiation ◽  
Cellular Expression ◽  
Galectin 3 ◽  
The Central Nervous System

Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and−9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,−3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N-glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6-N-acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.

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