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Article ; Online: From aversive associations to defensive programs: experience-dependent synaptic modifications in the central amygdala.

Penzo, Mario A / Moscarello, Justin M

2023 Volume 46, Issue 9, Page(s) 701–711

Abstract: Plasticity elicited by fear conditioning (FC) is thought to support the storage of aversive associative memories. Although work over the past decade has revealed FC-induced plasticity beyond canonical sites in the basolateral complex of the amygdala (BLA) ...

Abstract	Plasticity elicited by fear conditioning (FC) is thought to support the storage of aversive associative memories. Although work over the past decade has revealed FC-induced plasticity beyond canonical sites in the basolateral complex of the amygdala (BLA), it is not known whether modifications across distributed circuits make equivalent or distinct contributions to aversive memory. Here, we review evidence demonstrating that experience-dependent synaptic plasticity in the central nucleus of the amygdala (CeA) has a circumscribed role in memory expression per se, guiding the selection of defensive programs in response to acquired threats. We argue that the CeA may be a key example of a broader phenomenon by which synaptic plasticity at specific nodes of a distributed network makes a complementary contribution to distinct memory processes.
MeSH term(s)	Humans ; Central Amygdaloid Nucleus ; Fear/physiology ; Neuronal Plasticity/physiology ; Memory/physiology ; Affect
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural
ZDB-ID	282488-7
ISSN	1878-108X ; 0378-5912 ; 0166-2236
ISSN (online)	1878-108X
ISSN	0378-5912 ; 0166-2236
DOI	10.1016/j.tins.2023.06.006
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Zs.A 1442: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The central nucleus of the amygdala and the construction of defensive modes across the threat-imminence continuum.

Moscarello, Justin M / Penzo, Mario A

Nature neuroscience

2022 Volume 25, Issue 8, Page(s) 999–1008

Abstract: In nature, animals display defensive behaviors that reflect the spatiotemporal distance of threats. Laboratory-based paradigms that elicit specific defensive responses in rodents have provided valuable insight into the brain mechanisms that mediate the ... ...

Abstract	In nature, animals display defensive behaviors that reflect the spatiotemporal distance of threats. Laboratory-based paradigms that elicit specific defensive responses in rodents have provided valuable insight into the brain mechanisms that mediate the construction of defensive modes with varying degrees of threat imminence. In this Review, we discuss accumulating evidence that the central nucleus of the amygdala (CeA) plays a key role in this process. Specifically, we propose that the mutually inhibitory circuits of the CeA use a winner-takes-all strategy that supports transitioning across defensive modes and the execution of specific defensive behaviors to previously formed threat associations. Our proposal provides a conceptual framework in which seemingly divergent observations regarding CeA function can be interpreted and identifies various areas of priority for future research.
MeSH term(s)	Animals ; Central Amygdaloid Nucleus/physiology
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-022-01130-5
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Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Molecules affecting myelin stability: a novel hypothesis regarding the pathogenesis of multiple sclerosis.

Mastronardi, Fabrizio G / Moscarello, Mario A

Journal of neuroscience research

2005 Volume 80, Issue 3, Page(s) 301–308

Abstract: In this Mini-Review we present a new hypothesis in support of the neurodegenerative theory as a mechanism for the pathogenesis of multiple sclerosis (MS). The pathogenesis of MS results from changes in two distinct CNS compartments. These are the "myelin" ...

Abstract	In this Mini-Review we present a new hypothesis in support of the neurodegenerative theory as a mechanism for the pathogenesis of multiple sclerosis (MS). The pathogenesis of MS results from changes in two distinct CNS compartments. These are the "myelin" and "nonmyelin" compartments. The myelin compartment is where primary demyelination, amidst attempts at remyelination, is superseded in the CNS by ongoing disease. Recent evidence obtained via magnetic resonance imaging and spectroscopy techniques supports the view that the normal-appearing white matter (NAWM) in the MS brain is altered. Several biochemical changes in NAWM have been determined. These include the cationicity of myelin basic protein (MBP) as a result of the action of peptidyl argininedeiminase (PAD) activity converting arginyl residues to citrulline. The accompanying loss of positive charge makes myelin susceptible to vesiculation and MBP more susceptible to proteolytic activity. An increase of MBP autocatalysis in the MS brain might also contribute to the generation of immunodominant epitopes. Accompanying the destruction of myelin in the myelin compartment is the activation of astrocytes and microglia. These contribute to the inflammatory response and T-cell activation leading to autoimmunity. The complex environment that exists in the demyelinating brain also affects the "nonmyelin" compartment. The inappropriate up-regulation of molecules, including those of the Jagged-1-Notch-1 signal transduction pathway, affects oligodendrocyte precursor cell (OPC) differentiation. Other effectors of oligodendrocyte maturation include stathmin, a microtubule-destabilizing protein, which prevents healing in the demyelinating brain. The hypothesis we present suggests a therapeutic strategy that should 1) target the effectors within the myelin compartment and 2) enable resident OPC maturation in the nonmyelin compartment, allowing for effective repair of myelin loss. The net effect of this new therapeutic strategy is the modification of the disease environment and the stimulation of healing and repair.
MeSH term(s)	Animals ; Central Nervous System/immunology ; Central Nervous System/metabolism ; Central Nervous System/physiopathology ; Humans ; Multiple Sclerosis/etiology ; Multiple Sclerosis/immunology ; Multiple Sclerosis/metabolism ; Myelin Basic Protein/immunology ; Myelin Basic Protein/metabolism ; Myelin Proteins/immunology ; Myelin Proteins/metabolism ; Myelin Sheath/immunology ; Myelin Sheath/metabolism ; Nerve Fibers, Myelinated/immunology ; Nerve Fibers, Myelinated/metabolism ; Oligodendroglia/metabolism ; Recovery of Function/physiology
Chemical Substances	Myelin Basic Protein ; Myelin Proteins
Language	English
Publishing date	2005-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.20420
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Article: Interrogation of the Active Sites of Protein Arginine Deiminases (PAD1, -2, and -4) Using Designer Probes.

Bello, Angelica M / Wasilewski, Ewa / Wei, Lianhu / Moscarello, Mario A / Kotra, Lakshmi P

ACS medicinal chemistry letters

2013 Volume 4, Issue 2, Page(s) 249–253

Abstract: Protein arginine deiminases (PADs) are involved in a number of cellular pathways, and they catalyze the transformation of peptidyl arginine residue into a citrulline as part of post-translational modifications. To understand ligand preferences, a group ... ...

Abstract	Protein arginine deiminases (PADs) are involved in a number of cellular pathways, and they catalyze the transformation of peptidyl arginine residue into a citrulline as part of post-translational modifications. To understand ligand preferences, a group of probe molecules were investigated against PAD1, PAD2, and PAD4. These probe molecules carried a well-known covalent modifier of the catalytic cysteine residue, 2-chloroacetamidine moiety, which was tethered to an α-amino acid via a carbon linker. The chain length for the linker varied from 0 to 4. Time-dependent assays indicated that 2-chloroacetamidine (2CA) with no linker inhibited all PAD enzymes with a similar trend in the second-order rate constants, although with poor affinity. Among the other three probe molecules, compound 3 with a three-carbon linker exhibited the best second-order rate constants for optimal ligand reactivity with the binding site. These analyses provide insights into the relative patterns of covalent inactivation of PAD isozymes and the design of novel inhibitors targeting PAD enzymes as potential therapeutic targets.
Language	English
Publishing date	2013-01-15
Publishing country	United States
Document type	Journal Article
ISSN	1948-5875
ISSN	1948-5875
DOI	10.1021/ml300377d
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Article ; Online: Novel inhibitors of protein arginine deiminase with potential activity in multiple sclerosis animal model.

Wei, Lianhu / Wasilewski, Ewa / Chakka, Sai Kumar / Bello, Angelica M / Moscarello, Mario A / Kotra, Lakshmi P

Journal of medicinal chemistry

2013 Volume 56, Issue 4, Page(s) 1715–1722

Abstract: In multiple sclerosis (MS), myelin basic protein (MBP), critical for the maintenance of myelin compaction and protecting against degradation, is known to contain concentrations of the noncoded amino acid, "citrulline", in abnormal proportions. Peptidyl ... ...

Abstract	In multiple sclerosis (MS), myelin basic protein (MBP), critical for the maintenance of myelin compaction and protecting against degradation, is known to contain concentrations of the noncoded amino acid, "citrulline", in abnormal proportions. Peptidyl arginine deiminase (PAD) catalyzes the post-translational citrullination of proteins via the deimination of Arg residues. In the central nervous system, specifically PAD2 and PAD4, are the enzymes responsible for the citrullination. We used in silico screening of commercial libraries to find small molecules that would reversibly inhibit PAD4. An initial set of 10 diverse compounds was selected from the screen, and from these compounds, 3, 4, 6, and 8 showed promising inhibitory activities against PAD4 with Ki in the range of 115-153 μM. Compound 4 was selected to partake in an in vivo MOG EAE mouse model study to evaluate its effect in MS-like conditions. Results from the 24 day pilot mouse study showed an improved clinical outcome for mice being administered compound 4 compared to the control group. In brain, 4 treated mice showed a clear reduction in the CD3 +ve T cells. These results suggest that compound 4 may have potential utility and confirmed that noncovalent inhibitors of PAD enzymes can be developed as potential agents targeting MS pathology.
MeSH term(s)	Animals ; Brain/immunology ; Brain/pathology ; CD3 Complex/metabolism ; Catalytic Domain ; Computer Simulation ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Hydrolases/antagonists & inhibitors ; Imidazoles/chemical synthesis ; Imidazoles/chemistry ; Imidazoles/pharmacology ; Indoles/chemical synthesis ; Indoles/chemistry ; Indoles/pharmacology ; Mice ; Models, Molecular ; Multiple Sclerosis/drug therapy ; Pilot Projects ; Piperazines/chemical synthesis ; Piperazines/chemistry ; Piperazines/pharmacology ; Protein-Arginine Deiminases ; Pyridines/chemical synthesis ; Pyridines/chemistry ; Pyridines/pharmacology ; Pyrimidines/chemical synthesis ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Small Molecule Libraries/chemistry ; Stereoisomerism ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology ; Thiazoles/chemical synthesis ; Thiazoles/chemistry ; Thiazoles/pharmacology
Chemical Substances	CD3 Complex ; Imidazoles ; Indoles ; Piperazines ; Pyridines ; Pyrimidines ; Small Molecule Libraries ; Thiazoles ; Hydrolases (EC 3.-) ; Protein-Arginine Deiminases (EC 3.5.3.15) ; peptidylarginine deiminase type IV (EC 3.5.3.15)
Language	English
Publishing date	2013-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm301755q
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Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis.

Moscarello, Mario A / Mastronardi, Fabrizio G / Wood, D Denise

Neurochemical research

2007 Volume 32, Issue 2, Page(s) 251–256

Abstract: The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The ... ...

Abstract	The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was increased in MS normal-appearing white matter. The mechanism responsible for this increase involved hypomethylation of the promoter region in the PAD 2 gene in MS, but no change (compared to normal) was found in thymus tissue DNA from the same MS patients. In addition, no change was observed in other neurological diseases, including Alzheimer's, Parkinson's, and Huntington's. We propose that citrullinated MBP, resulting from elevated levels of PAD 2 represents an important biochemical pathway in the pathogenesis of MS.
MeSH term(s)	Apoptosis ; Citrulline/physiology ; Humans ; Hydrolases/metabolism ; Methylation ; Multiple Sclerosis/enzymology ; Multiple Sclerosis/etiology ; Myelin Basic Protein/metabolism ; Oligodendroglia/physiology ; Protein Conformation/drug effects ; Protein Processing, Post-Translational ; Protein-Arginine Deiminases
Chemical Substances	Myelin Basic Protein ; Citrulline (29VT07BGDA) ; Hydrolases (EC 3.-) ; Protein-Arginine Deiminases (EC 3.5.3.15)
Language	English
Publishing date	2007-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-006-9144-5
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Article ; Online: Myelin basic protein undergoes a broader range of modifications in mammals than in lower vertebrates.

Zhang, Chunchao / Walker, Angela K / Zand, Robert / Moscarello, Mario A / Yan, Jerry Mingtao / Andrews, Philip C

Journal of proteome research

2012 Volume 11, Issue 10, Page(s) 4791–4802

Abstract: Myelin basic protein (MBP) is an important component of the myelin sheath surrounding neurons, and it is directly affected in demyelinating diseases. MBP contains a relatively large number of post-translational modifications (PTMs), which have been ... ...

Abstract	Myelin basic protein (MBP) is an important component of the myelin sheath surrounding neurons, and it is directly affected in demyelinating diseases. MBP contains a relatively large number of post-translational modifications (PTMs), which have been reported to play a role in multiple sclerosis, while MBPs from lower vertebrates have been reported to be incapable of inducing multiple sclerosis or allergic encephalitis. This study reveals the extent of differences in PTM patterns for mammalian and nonmammalian MBPs. This included intact mass and de novo sequence analysis of approximately 85% of rattlesnake MBP, the first reptile MBP to be characterized, and of bovine MBP. We identified 12 PTMs at 11 sites in the five bovine MBP charge components, which include both previously reported and novel modifications. The most notable modification is an acetylation of lysine 121. Other modifications found in bovine MBP include N-terminal acetylation in components C1, C2, and C3; oxidation of methionine 19 in all five components; all charge isomers having both a mono- and dimethylated (symmetric) arginine at position 106; deimination in arginines 23 and 47 found only in component C8b; deimination of arginine 96 and deamidation in glutamine 102 found in components C2, C3, C8a, and C8b; phosphorylation in threonine 97 restricted to charge components C2 and C3; deimination in arginine 161 only found in component C3; deamidation of glutamine 120 was only observed in C3. All four deiminated arginines and one acetylated lysine were first experimentally revealed in this study for bovine MBP. Mascot database searching combined with de novo sequence analysis of rattlesnake MBP provided more than 85% sequence coverage. A few PTMs were also revealed in rattlesnake MBP: mono- and dimethylated Arg, protein N-terminal acetylation, and deiminated Arg. Overall, snake MBP was found to undergo less modification than bovine MBP on the basis of the mass heterogeneity of the intact protein, the bottom-up structure analysis, and the limited complexity of rattlesnake MBP chromatography. The combined data from this study and information from previous studies extend the known MBP PTMs, and PTMs unique to higher vertebrates are proposed.
MeSH term(s)	Acetylation ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Brain/metabolism ; Cattle ; Conserved Sequence ; Crotalus ; Methylation ; Molecular Sequence Data ; Myelin Basic Protein/chemistry ; Myelin Basic Protein/metabolism ; Peptide Fragments/chemistry ; Phosphorylation ; Protein Processing, Post-Translational ; Reptilian Proteins/chemistry ; Reptilian Proteins/metabolism ; Sequence Analysis, Protein ; Tandem Mass Spectrometry
Chemical Substances	Myelin Basic Protein ; Peptide Fragments ; Reptilian Proteins
Language	English
Publishing date	2012-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/pr201196e
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Article: Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope.

D'Souza, Cheryl A / Moscarello, Mario A

Neurochemical research

2006 Volume 31, Issue 8, Page(s) 1045–1054

Abstract: Charge microheterogeneity of myelin basic protein is known to affect its conformation and function. Here, the citrullinated myelin basic protein charge isomer, component-8, was shown to be more susceptible to stromelysin-1 cleavage than myelin basic ... ...

Abstract	Charge microheterogeneity of myelin basic protein is known to affect its conformation and function. Here, the citrullinated myelin basic protein charge isomer, component-8, was shown to be more susceptible to stromelysin-1 cleavage than myelin basic protein component-1. Since levels of component-8 are increased in multiple sclerosis brain, the increased susceptibility of component-8 to proteolytic digestion may play a role in the pathogenesis of multiple sclerosis. Interestingly, component-1 isolated from multiple sclerosis patients was digested at a faster rate by stromelysin-1 than component-1 isolated from normal individuals. The reason for this difference is not clear, but likely reflects conformational differences between the two proteins as a result of post-translational modifications. Stromelysin-1 was able to cleave myelin basic protein in the presence of lipids and within the context of myelin and released several peptides including peptides containing the immunodominant epitope.
MeSH term(s)	Animals ; Cattle ; Humans ; Immunodominant Epitopes ; Matrix Metalloproteinase 3/metabolism ; Multiple Sclerosis/metabolism ; Myelin Basic Protein/chemistry ; Myelin Basic Protein/metabolism ; Myelin Sheath/chemistry ; Myelin Sheath/metabolism ; Peptide Fragments/chemistry ; Peptide Fragments/genetics ; Peptide Fragments/metabolism ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism
Chemical Substances	Immunodominant Epitopes ; Myelin Basic Protein ; Peptide Fragments ; Protein Isoforms ; Matrix Metalloproteinase 3 (EC 3.4.24.17)
Language	English
Publishing date	2006-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-006-9116-9
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Article: The up-regulation of stromelysin-1 (MMP-3) in a spontaneously demyelinating transgenic mouse precedes onset of disease.

D'Souza, Cheryl A / Mak, Baldwin / Moscarello, Mario A

The Journal of biological chemistry

2002 Volume 277, Issue 16, Page(s) 13589–13596

Abstract: The matrix metalloproteinases (MMPs) are a family of endoproteinases that degrade various components of the extracellular matrix and have been implicated in the pathogenesis of multiple sclerosis. To determine whether up-regulation of MMP-3, or ... ...

Abstract	The matrix metalloproteinases (MMPs) are a family of endoproteinases that degrade various components of the extracellular matrix and have been implicated in the pathogenesis of multiple sclerosis. To determine whether up-regulation of MMP-3, or stromelysin-1, was a causative factor during the development of demyelination, we have examined the expression of MMP-3 mRNA and protein in brain tissue of a spontaneously demyelinating mouse model overexpressing DM20 (ND4 line) prior to and during the progression of disease. Stromelysin-1, but not other MMP mRNA was elevated approximately 10-fold in transgenic mice between 5 days and 1 month of age, more than 2 months before the onset of disease, and was coordinately expressed with the DM20 transgene. Stromelysin-1 protein levels were also up-regulated as was tissue inhibitor of metalloproteinase-1 (TIMP-1), an in vivo regulator of stromelysin-1 mRNA. When we crossed our ND4 mice with a line of transgenic mice overexpressing TIMP-1 in brain, clinical signs in these mice were attenuated, and the level of stromelysin-1 protein was reduced. Thus, in this transgenic model of demyelinating disease up-regulation of DM20, MMP-3, and TIMP-1 represent important changes in the chemical pathogenesis in brain, which precede the onset of disease.
MeSH term(s)	Age Factors ; Animals ; Blotting, Northern ; Blotting, Western ; Brain/metabolism ; DNA, Complementary/metabolism ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Humans ; Hydrogen-Ion Concentration ; Matrix Metalloproteinase 3/biosynthesis ; Mice ; Mice, Transgenic ; Myelin Proteolipid Protein/metabolism ; Myelin Sheath/metabolism ; Myelin Sheath/physiology ; Nerve Tissue Proteins ; RNA/metabolism ; RNA, Messenger/metabolism ; Time Factors ; Tissue Distribution ; Tissue Inhibitor of Metalloproteinase-1/metabolism ; Transgenes ; Up-Regulation
Chemical Substances	DNA, Complementary ; Myelin Proteolipid Protein ; Nerve Tissue Proteins ; Plp1 protein, mouse ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-1 ; RNA (63231-63-0) ; Matrix Metalloproteinase 3 (EC 3.4.24.17)
Language	English
Publishing date	2002-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M108817200
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Article: Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated.

Mastronardi, Fabrizio G / Noor, Abdul / Wood, D Denise / Paton, Tara / Moscarello, Mario A

Journal of neuroscience research

2007 Volume 85, Issue 9, Page(s) 2006–2016

Abstract: In previous studies, we documented increased citrullinated myelin basic protein (MBP) was present in MBP isolated from multiple sclerosis (MS) normal appearing white matter (NAWM). This increase was due to the myelin enzyme peptidyl argininedeiminase 2 ( ... ...

Abstract	In previous studies, we documented increased citrullinated myelin basic protein (MBP) was present in MBP isolated from multiple sclerosis (MS) normal appearing white matter (NAWM). This increase was due to the myelin enzyme peptidyl argininedeiminase 2 (PAD2). In this study, we show that methylation of cytosine of the PAD2 promoter in DNA from MS NAWM was decreased to one-third of the level of that in DNA from normal white matter. The PAD2 promoter in DNA from thymus obtained from the same MS patients and white matter DNA from Alzheimer's, Huntington's, and Parkinson's was not hypomethylated. DNA demethylase activity in supernatants prepared from NAWM of MS patients was 2-fold higher than the DNA demethylase from normal, Alzheimer's, Huntington's and Parkinson's disease white matter. The amount of PAD2 enzyme and citrullinated MBP was increased in MS NAWM. The decreased methylation of cytosines in the PAD2 promoter may explain the increased synthesis of PAD2 protein that is responsible for the increased amount of citrullinated MBP, which in turn results in loss of myelin stability in MS brain.
MeSH term(s)	5-Methylcytosine/metabolism ; Blotting, Western ; Brain/enzymology ; Citrulline/metabolism ; CpG Islands/physiology ; DNA/biosynthesis ; DNA/genetics ; DNA, Single-Stranded/metabolism ; Fluorescent Antibody Technique ; Humans ; Hydrolases/metabolism ; Methylation ; Multiple Sclerosis/enzymology ; Myelin Basic Protein/metabolism ; Promoter Regions, Genetic/genetics ; Protein-Arginine Deiminases ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfites/pharmacology ; Thymus Gland/metabolism
Chemical Substances	DNA, Single-Stranded ; Myelin Basic Protein ; Sulfites ; Citrulline (29VT07BGDA) ; 5-Methylcytosine (6R795CQT4H) ; DNA (9007-49-2) ; Hydrolases (EC 3.-) ; PADI2 protein, human (EC 3.5.3.15) ; Protein-Arginine Deiminases (EC 3.5.3.15)
Language	English
Publishing date	2007-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.21329
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Full text online

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In stock of ZB MED Cologne/Königswinter

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