Page last updated: 2024-10-24

positive regulation of neuroinflammatory response

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of neuroinflammatory response. [GOC:aruk, GOC:bc]

Positive regulation of neuroinflammatory response is a complex biological process involving a cascade of events that ultimately leads to the activation and recruitment of immune cells to the central nervous system (CNS) in response to various stimuli, such as infection, injury, or autoimmune disorders. The process is tightly regulated to ensure an appropriate and timely response, preventing excessive inflammation that can lead to neuronal damage and neurological dysfunction.

Here is a detailed description of the process:

1. **Stimulus Recognition:** The initial step involves the recognition of a harmful stimulus by cells in the CNS, such as microglia, astrocytes, and neurons. These cells express various pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), that can detect pathogen-associated molecular patterns (PAMPs) from invading pathogens or damage-associated molecular patterns (DAMPs) released from injured cells.

2. **Signal Transduction:** Upon recognition of the stimulus, PRRs initiate intracellular signaling cascades that activate transcription factors, such as NF-κB and AP-1. These transcription factors promote the expression of various pro-inflammatory cytokines, chemokines, and adhesion molecules.

3. **Cytokine and Chemokine Production:** Activated immune cells release a variety of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IFN-γ, as well as chemokines, such as CCL2 and CXCL10. These molecules act as signaling messengers that attract and activate other immune cells, such as neutrophils, macrophages, and lymphocytes.

4. **Immune Cell Recruitment:** Pro-inflammatory cytokines and chemokines act on the blood vessels in the CNS, increasing vascular permeability and promoting the adherence of immune cells to the endothelium. This process, known as leukocyte extravasation, allows immune cells to migrate from the blood into the CNS parenchyma.

5. **Immune Cell Activation:** Once recruited to the CNS, immune cells become activated and release additional pro-inflammatory mediators, contributing to the amplification of the inflammatory response. Activated microglia, the resident immune cells of the CNS, phagocytose pathogens and cellular debris, while neutrophils and macrophages release enzymes and reactive oxygen species that kill invading pathogens and clear debris.

6. **Resolution of Inflammation:** After the initial inflammatory response, mechanisms are initiated to resolve inflammation and restore tissue homeostasis. This process involves the production of anti-inflammatory cytokines, such as IL-10 and TGF-β, which dampen the inflammatory response and promote tissue repair.

7. **Regulation of Neuroinflammation:** The positive regulation of neuroinflammatory response is tightly controlled to ensure an appropriate and timely response. Various mechanisms contribute to this regulation, including:

- **Negative feedback loops:** Pro-inflammatory cytokines can trigger the production of anti-inflammatory cytokines, creating negative feedback loops that help to dampen the inflammatory response.

- **Immune tolerance:** The CNS maintains immune tolerance to prevent autoimmune reactions against self-antigens.

- **Blood-brain barrier (BBB):** The BBB acts as a physical barrier between the blood and the CNS, restricting the entry of immune cells and inflammatory mediators.

Dysregulation of the positive regulation of neuroinflammatory response can lead to chronic inflammation, neuronal damage, and neurological disorders. Understanding this complex process is crucial for developing therapeutic strategies for treating neuroinflammatory diseases.'
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Proteins (4)

ProteinDefinitionTaxonomy
Neutrophil collagenaseA neutrophil collagenase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P22894]Homo sapiens (human)
Interleukin-6An interleukin-6 that is encoded in the genome of human. [PRO:JAN, UniProtKB:P05231]Homo sapiens (human)
Interleukin-1 betaAn interleukin-1 beta that is encoded in the genome of human. [PRO:CNA, UniProtKB:P01584]Homo sapiens (human)
Tumor necrosis factorA tumor necrosis factor that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (48)

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
nafamostatnafamostat: inhibitor of trypsin, plasmin, pancreatic kallikrein, plasma kallikrein & thrombin; strongly inhibits esterolytic activities of C1r & C1 esterase complement-mediated hemolysis; antineoplasticbenzoic acids;
guanidines
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)
tiludronic acidtiludronic acid: a bone resorption inhibitor; an antihypercalcemic agent; used in the tratment of Paget's disease; used in the treatment and prevention of osteoporosis; structure given in first sourceorganochlorine compound
bergeninbergenin: RN refers to (2R-(2alpha,3beta,4alpha,4aalpha,10bbeta))-isomer; structuretrihydroxybenzoic acidmetabolite
zoledronic acidzoledronic acid : An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.

Zoledronic Acid: An imidobisphosphonate inhibitor of BONE RESORPTION that is used for the treatment of malignancy-related HYPERCALCEMIA; OSTEITIS DEFORMANS; and OSTEOPOROSIS.
1,1-bis(phosphonic acid);
imidazoles
bone density conservation agent
piloty's acidPiloty's acid: structure in first sourcesulfonamide
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
n-(2-isobutyl-3-(n'-hydroxycarbonylamido)propanoyl)-o-methyltyrosinemethylamideN-(2-isobutyl-3-(N'-hydroxycarbonylamido)propanoyl)-O-methyltyrosinemethylamide: RN given refers to the (S-(R*,S*))-isomer
ilomastatCS 610: matrix metalloproteinase inhibitor; structure in first source

ilomastat : An N-acyl-amino acid obtained by formal condensation of the carboxy group of (2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the amino group of N-methyl-L-tryptophanamide. A cell permeable broad-spectrum matrix metalloproteinase (MMP) inhibitor
hydroxamic acid;
L-tryptophan derivative;
N-acyl-amino acid
anti-inflammatory agent;
antibacterial agent;
antineoplastic agent;
EC 3.4.24.24 (gelatinase A) inhibitor;
neuroprotective agent
birb 796aromatic ether;
morpholines;
naphthalenes;
pyrazoles;
ureas
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
immunomodulator
3-((benzyl)(methylaminocarbonyl)methylaminocarbonyl)n-hydroxy-5-methylhexanamide3-((benzyl)(methylaminocarbonyl)methylaminocarbonyl)N-hydroxy-5-methylhexanamide: structure in first source
2-(4-aminophenyl)benzothiazole2-(4-aminophenyl)benzothiazole: an agent with selective profile of in vitro anti-tumour activity; structure in first source
cgs 27023aCGS 27023A: a matrix metalloproteinase inhibitor
prinomastatprinomastat : A hydroxamic acid that is (3S)-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide in which the hydrogen attached to the thiomorpholine nitrogen has been replaced by a [4-(pyridin-4-yloxy)phenyl]sulfonyl group. It is a selective inhibitor with of matrix metalloproteinases (MMPs) 2, 3, 9, 13, and 14.

prinomastat: a diazepine-based hydroxamic acid inhibitor; matrix metalloproteinase (MMP) inhibitor; angiogenesis inhibitor;
aromatic ether;
hydroxamic acid;
pyridines;
sulfonamide;
thiomorpholines
antineoplastic agent;
EC 3.4.24.35 (gelatinase B) inhibitor;
matrix metalloproteinase inhibitor
ganoderic acid atriterpenoid
ganoderiol fganoderiol F: a ganoderma triterpene from Ganoderma amboinense; structure in first sourcetriterpenoid
1-(phenylmethyl)benzimidazolebenzimidazoles
2-[(4-phenylphenyl)sulfonylamino]pentanedioic acidglutamic acid derivative
rs-130830RS-130830: orally-active broad-spectrum matrix metalloproteinase inhibitor
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
n-acetyltyrosyl-valyl-alanyl-aspartyl aldehyde
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
batimastatbatimastat : A secondary carboxamide resulting from the formal condensation of the carboxy group of (2S,3R)-5-methyl-3-{[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl}-2-[(thiophen-2-ylsulfanyl)methyl]hexanoic acid with the amino group of hydroxylamine. It a broad-spectrum matrix metalloprotease inhibitor.

batimastat: structure given in first source; a synthetic matrix metalloproteinase inhibitor
hydroxamic acid;
L-phenylalanine derivative;
organic sulfide;
secondary carboxamide;
thiophenes;
triamide
angiogenesis inhibitor;
antineoplastic agent;
matrix metalloproteinase inhibitor
ik 682IK 682: inhibits TNF-alpha converting enzyme; structure in first sourcehydroxamic acid;
pyrrolidin-2-ones;
quinolines
(11c)cgs 25966
ro 32-3555Ro 32-3555: structure given in first source
sb 3ct compoundSB 3CT compound: a matrix metalloproteinase-2 inhibitor; structure in first sourcearomatic ether
pd 166793
sc 78080
arp-100
N(2)-([biphenyl]-4-ylsulfonyl)-N-hydroxy-N(2)-isopropoxy-D-valinamideN(2)-([biphenyl]-4-ylsulfonyl)-N-hydroxy-N(2)-isopropoxy-D-valinamide : A hydroxamic acid that is N-hydroxy-D-valinamide in which the alpha-amino group has been substituted by isopropoxy and [biphenyl]-4-ylsulfonyl groups. A selective matrix metalloproteinase-2 (MMP-2) inhibitor, it is one of the most potent inducers of autophagy. Its physiological roles include angiogenesis, cancer metastasis, embryogenesis, tissue remodeling in development, and wound healing.D-valine derivative;
hydroxamic acid
antineoplastic agent;
autophagy inducer;
EC 3.4.24.24 (gelatinase A) inhibitor;
melanin synthesis inhibitor
bms-566394BMS-566394: structure in first source
berkeleydioneberkeleydione : A meroterpenoid found in Penicillium rubrum. It has been shown to exhibit inhibitory activity against caspase-1.

berkeleydione: polyketide-terpenoid metabolite, isolated from a Penicillium sp.; structure in first source
beta-diketone;
cyclic terpene ketone;
meroterpenoid;
methyl ester;
organic heterotetracyclic compound;
terpene lactone;
tertiary alcohol;
tertiary alpha-hydroxy ketone
antineoplastic agent;
cysteine protease inhibitor;
Penicillium metabolite
ganoderic acid fganoderic acid F: isolated from Ganoderma lucidum; structure in first sourcetriterpenoid
grassystatin agrassystatin A: isolated from a cyanobacterium, identified as Lyngbya cf.; structure in first source
bi 653048 bs h3po4BI 653048 BS H3PO4: structure in first source
tetracyclinetetracycline : A broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria.

Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.
ganoderic acid c2ganoderic acid C2: from the fruiting body of Ganoderma; structure in first sourcetriterpenoid
2-[(4-chlorophenyl)methylthio]-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-onearyl sulfide
2-[(4-methoxyphenyl)methylthio]-6-methyl-1H-pyrimidin-4-onemethoxybenzenes
4-[[(4-oxo-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-2-yl)thio]methyl]benzoic acid methyl esterbenzoate ester