Page last updated: 2024-10-24

negative regulation of myelination

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of the formation of a myelin sheath around nerve axons. [GOC:mah]

Negative regulation of myelination is a crucial process that ensures precise control over the formation and maintenance of the myelin sheath, a fatty covering that insulates nerve fibers and facilitates efficient signal transmission in the nervous system. This intricate process involves a delicate balance of molecular interactions, ensuring that myelination is tightly regulated and occurs only when and where it is needed.

Myelination is a complex process that involves the coordinated action of multiple cell types, including oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). These glial cells produce myelin, which wraps around axons, forming a multi-layered sheath.

The negative regulation of myelination is essential to prevent excessive or inappropriate myelination, which could disrupt neuronal function. Several mechanisms contribute to this regulation:

**1. Transcriptional Regulation:**
- Transcription factors play a key role in controlling the expression of genes involved in myelination. Repressor proteins bind to specific DNA sequences, preventing the transcription of genes encoding myelination-related proteins. This downregulation of gene expression limits the production of myelin components.

**2. Signaling Pathways:**
- Various signaling pathways, such as the Notch and Wnt pathways, are involved in negative regulation of myelination. These pathways activate repressor proteins or inhibit the activity of pro-myelinating factors, thereby controlling myelination timing and extent.

**3. Cell-Cell Interactions:**
- Interactions between glial cells and neurons are critical for regulating myelination. Signals from neurons, such as inhibitory factors or the absence of specific stimulatory cues, can prevent glial cells from initiating or continuing myelination.

**4. Environmental Factors:**
- External factors, such as inflammation or hypoxia, can negatively regulate myelination. These stressors can trigger signaling pathways that inhibit myelination or induce the production of factors that interfere with myelin formation.

**5. Inhibitor Molecules:**
- Specific molecules, such as myelin-associated inhibitors (MAIs), act as inhibitors of myelination. These molecules are expressed by neurons or glial cells and can directly block the formation or maintenance of the myelin sheath.

**6. Degradation and Remodeling:**
- Myelin is not static and can be degraded or remodeled in response to various signals. This process involves enzymes that break down myelin components, ensuring that myelin is removed when needed and that the myelin sheath is constantly adapted to changes in neuronal activity.

The negative regulation of myelination is a tightly controlled process that is critical for the proper development and function of the nervous system. Dysregulation of this process can lead to various neurological disorders, including multiple sclerosis (MS), in which the myelin sheath is damaged and destroyed, leading to impaired nerve conduction and neurological dysfunction. Understanding the mechanisms underlying the negative regulation of myelination is crucial for developing strategies to prevent and treat these diseases.'
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Proteins (3)

ProteinDefinitionTaxonomy
Eukaryotic translation initiation factor 2-alpha kinase 3A eukaryotic translation initiation factor 2-alpha kinase 3 that is encoded in the genome of human. [PRO:CNx, UniProtKB:Q9NZJ5]Homo sapiens (human)
Dipeptidyl peptidase 1A dipeptidyl peptidase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P53634]Homo sapiens (human)
Tumor necrosis factorA tumor necrosis factor that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (35)

CompoundDefinitionClassesRoles
mesalaminemesalamine : A monohydroxybenzoic acid that is salicylic acid substituted by an amino group at the 5-position.

Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)
amino acid;
aromatic amine;
monocarboxylic acid;
monohydroxybenzoic acid;
phenols
non-steroidal anti-inflammatory drug
way 151693
pentoxifyllineoxopurine
4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.methoxybenzenes
roliprampyrrolidin-2-onesantidepressant;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor
sulfasalazinesulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position.

Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)
bergeninbergenin: RN refers to (2R-(2alpha,3beta,4alpha,4aalpha,10bbeta))-isomer; structuretrihydroxybenzoic acidmetabolite
Pyrrolidine-1-carbonitrilepyrrolidines
marimastatmarimastat : A secondary carboxamide resulting from the foraml condensation of the carboxy group of (2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the alpha-amino group of N,3-dimethyl-L-valinamide.

marimastat: a matrix metalloproteinase inhibitor active in patients with advanced carcinoma of the pancreas, prostate, or ovary
hydroxamic acid;
secondary carboxamide
antineoplastic agent;
matrix metalloproteinase inhibitor
e 64E 64: cysteine protease inhibitor of microbial origin, which inhibits cathepsin B (EC 3.4.22.1) and cathepsin L (EC 3.4.22.-)dicarboxylic acid monoamide;
epoxy monocarboxylic acid;
guanidines;
L-leucine derivative;
zwitterion
antimalarial;
antiparasitic agent;
protease inhibitor
canertinibmonochlorobenzenes;
morpholines;
organofluorine compound;
quinazolines
antineoplastic agent;
tyrosine kinase inhibitor
birb 796aromatic ether;
morpholines;
naphthalenes;
pyrazoles;
ureas
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
immunomodulator
ganoderic acid atriterpenoid
ganoderiol fganoderiol F: a ganoderma triterpene from Ganoderma amboinense; structure in first sourcetriterpenoid
1-(phenylmethyl)benzimidazolebenzimidazoles
luteolin-7-glucosideluteolin 7-O-beta-D-glucoside : A glycosyloxyflavone that is luteolin substituted by a beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage.

luteolin-7-glucoside: has both antiasthmatic and antineoplastic activities; has 3C protease inhibitory activity; isolated from Ligustrum lucidum
beta-D-glucoside;
glycosyloxyflavone;
monosaccharide derivative;
trihydroxyflavone
antioxidant;
plant metabolite
apigetrinapigenin 7-O-beta-D-glucoside : A glycosyloxyflavone that is apigenin substituted by a beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage.

apigetrin: structure given in first source
beta-D-glucoside;
dihydroxyflavone;
glycosyloxyflavone;
monosaccharide derivative
antibacterial agent;
metabolite;
non-steroidal anti-inflammatory drug
calycosin-7-o-beta-d-glucopyranosidecalycosin-7-O-beta-D-glucoside : A glycosyloxyisoflavone that is calycosin substituted by a beta-D-glucopyranosyl residue at position at 7 via a glycosidic linkage.

calycosin-7-O-beta-D-glucoside: from Radix Astragali
4'-methoxyisoflavones;
7-hydroxyisoflavones 7-O-beta-D-glucoside;
hydroxyisoflavone;
monosaccharide derivative
spd-304SPD-304: structure in first source
odanacatibodanacatib: a selective inhibitor of cathepsin K for the treatment of post-menopausal osteoporosis; structure in first source
bibw 2992aromatic ether;
enamide;
furans;
monochlorobenzenes;
organofluorine compound;
quinazolines;
secondary carboxamide;
tertiary amino compound
antineoplastic agent;
tyrosine kinase inhibitor
ganoderic acid fganoderic acid F: isolated from Ganoderma lucidum; structure in first sourcetriterpenoid
entrectinibentrectinib : A member of the class of indazoles that is 1H-indazole substituted by [4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzoyl]amino and 3,5-difluorobenzyl groups at positions 3 and 5, respectively. It is a potent inhibitor of TRKA, TRKB, TRKC, ROS1, and ALK (IC50 values of 0.1 to 1.7 nM), and used for the treatment of NTRK, ROS1 and ALK gene fusion-positive solid tumours.

entrectinib: inhibits TRK, ROS1, and ALK receptor tyrosine kinases; structure in first source
benzamides;
difluorobenzene;
indazoles;
N-methylpiperazine;
oxanes;
secondary amino compound;
secondary carboxamide
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
6-(3,5-difluoroanilino)-9-ethyl-2-purinecarbonitrile6-aminopurines
6-(3,5-difluoroanilino)-9-(2,2-difluoroethyl)-2-purinecarbonitrile6-aminopurines
9-(3,5-difluorophenyl)-6-(ethylamino)-2-purinecarbonitrileimidazoles
grassystatin agrassystatin A: isolated from a cyanobacterium, identified as Lyngbya cf.; structure in first source
thiopental sodiumorganochlorine compound;
piperazines;
pyrimidines
antineoplastic agent;
tyrosine kinase inhibitor
nms p937NMS P937: a polo-like kinase 1 inhibitor; structure in first source
nms-p118NMS-P118: a PARP-1 inhibitor; structure in first source
gsk2656157biaryl;
indoles;
methylpyridines;
organofluorine compound;
pyrrolopyrimidine;
tertiary carboxamide
antineoplastic agent;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor;
PERK inhibitor
7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1h-indol-5-yl)-7h-pyrrolo(2,3-d)pyrimidin-4-amine7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine: inhibits protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK); structure in first source
ganoderic acid c2ganoderic acid C2: from the fruiting body of Ganoderma; structure in first sourcetriterpenoid
osimertinibosimertinib : A member of the class of aminopyrimidines that is 4-(1-methylindol-3-yl)pyrimidin-2-amine in which one of the amino hydrogens is replaced by a 2-methoxy-4-[2-(dimethylamino)ethyl](methyl)amino-5-acrylamidophenyl group. Used (as the mesylate salt) for treatment of EGFR T790M mutation positive non-small cell lung cancer.

osimertinib: an EGFR tyrosine kinase inhibitor
acrylamides;
aminopyrimidine;
biaryl;
indoles;
monomethoxybenzene;
secondary amino compound;
secondary carboxamide;
substituted aniline;
tertiary amino compound
antineoplastic agent;
epidermal growth factor receptor antagonist
nms-e973NMS-E973: structure in first source