Target type: biologicalprocess
Any process that decreases the rate, frequency or extent of the establishment of the blood-brain barrier, a selectively permeable structural and functional barrier that exists between the capillaries and the brain. [GOC:dph, GOC:tb]
The blood-brain barrier (BBB) is a highly selective barrier that protects the central nervous system (CNS) from harmful substances in the bloodstream. Formation and maintenance of this barrier is a complex process involving interactions between endothelial cells, pericytes, astrocytes, and microglia. Negative regulation of the BBB establishment refers to mechanisms that inhibit or dampen the formation of this barrier, thereby potentially increasing permeability and allowing for the passage of substances that would otherwise be restricted.
Several mechanisms contribute to the negative regulation of BBB establishment, including:
1. **Signaling pathways:**
- **TGF-β signaling:** Transforming growth factor-beta (TGF-β) signaling can negatively regulate BBB formation by suppressing tight junction formation and increasing permeability.
- **VEGF signaling:** Vascular endothelial growth factor (VEGF) can promote angiogenesis and increase BBB permeability, potentially disrupting barrier integrity.
- **TNF-α signaling:** Tumor necrosis factor-alpha (TNF-α) can trigger inflammation and disrupt the BBB, increasing permeability.
2. **Cell-cell interactions:**
- **Endothelial cell-pericyte interactions:** Disruptions in the communication between endothelial cells and pericytes can weaken the BBB and increase permeability.
- **Astrocyte-endothelial cell interactions:** Dysfunctional astrocytes can release factors that disrupt BBB integrity.
- **Microglia-endothelial cell interactions:** Activation of microglia, often triggered by inflammation, can lead to BBB dysfunction and increased permeability.
3. **Genetic factors:**
- **Mutations in genes involved in tight junction formation:** Mutations in genes that encode for tight junction proteins can compromise BBB integrity and increase permeability.
- **Mutations in genes that regulate vascular development:** Mutations in genes involved in vascular development can lead to abnormal BBB formation and increased permeability.
4. **Environmental factors:**
- **Infections:** Infections can trigger inflammatory responses that damage the BBB and increase permeability.
- **Toxins:** Exposure to toxins can disrupt BBB integrity and increase permeability.
- **Stress:** Chronic stress can lead to BBB dysfunction and increased permeability.
The negative regulation of BBB establishment can have significant implications for brain health. Increased permeability of the BBB can contribute to neuroinflammation, neurodegeneration, and the development of neurological disorders. Understanding the mechanisms involved in negative regulation of BBB establishment is crucial for developing strategies to protect the brain from damage and disease.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| Transient receptor potential cation channel subfamily V member 1 | A transient receptor potential cation channel TRPV1 that is encoded in the genome of human. [PRO:CNA, UniProtKB:Q8NER1] | Homo sapiens (human) |
| Alpha-tocopherol transfer protein | An alpha-tocopherol transfer protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49638] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 2-aminoethoxydiphenyl borate | 2-aminoethoxydiphenyl borate: is a novel membrane-penetrable modulator and transient receptor potential channel blocker; structure in first source; do not confuse with 2-APB cpd 2-aminoethoxydiphenylborane : An organoboron compound that is diphenylborane in which the borane hydrogen is replaced by a 2-aminoethoxy group. | organoboron compound; primary amino compound | calcium channel blocker; IP3 receptor antagonist; potassium channel opener |
| benzyl isothiocyanate | benzyl isothiocyanate: inhibits carcinogen-induced neoplasia; structure in Negwer, 5th ed, #715; also promotes urinary bladder carcinoma | benzenes; isothiocyanate | antibacterial drug |
| cannabinol | Cannabinol: A physiologically inactive constituent of Cannabis sativa L. | dibenzopyran | |
| palmidrol | palmidrol: a cannabinoid receptor-inactive eCB-related molecule used as prophylactic in helping to prevent respiratory viral infection palmitoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of palmitic (hexadecanoic) acid. | endocannabinoid; N-(long-chain-acyl)ethanolamine; N-(saturated fatty acyl)ethanolamine | anti-inflammatory drug; anticonvulsant; antihypertensive agent; neuroprotective agent |
| allyl isothiocyanate | allyl isothiocyanate : An isothiocyanate with the formula CH2=CHCH2N=C=S. A colorless oil with boiling point 152degreeC, it is responsible for the pungent taste of mustard, horseradish, and wasabi. allyl isothiocyanate: used in the manufacture of flavors, war gases; medical use as a counterirritant; structure | alkenyl isothiocyanate; isothiocyanate | antimicrobial agent; antineoplastic agent; apoptosis inducer; lachrymator; metabolite |
| citronellol | citronellol : A monoterpenoid that is oct-6-ene substituted by a hydroxy group at position 1 and methyl groups at positions 3 and 7. citronellol: alcohol form of citronellal; found in rose oil; RN given refers to parent cpd without isomeric designation; structure insect repellent : An insecticide that acts as a repellent to insects. | monoterpenoid | plant metabolite |
| citronellyl acetate | citronellol acetate : A monoterpenoid that is the acetate ester of citronellol. It has been isolated from Citrus hystrix. citronellyl acetate: RN given refers to cpd without isomeric designation | acetate ester; monoterpenoid | plant metabolite |
| d-alpha tocopherol | (R,R,R)-alpha-tocopherol : An alpha-tocopherol that has R,R,R configuration. The naturally occurring stereoisomer of alpha-tocopherol, it is found particularly in sunflower and olive oils. tocopherol : A collective name for a group of closely related lipids that contain a chroman-6-ol nucleus substituted at position 2 by a methyl group and by a saturated hydrocarbon chain consisting of three isoprenoid units. They are designated as alpha-, beta-, gamma-, and delta-tocopherol depending on the number and position of additional methyl substituents on the aromatic ring. Tocopherols occur in vegetable oils and vegetable oil products, almost exclusively with R,R,R configuration. Tocotrienols differ from tocopherols only in having three double bonds in the hydrocarbon chain. vitamin E : Any member of a group of fat-soluble chromanols that exhibit biological activity against vitamin E deficiency. The vitamers in this class consists of a chroman-6-ol core which is substituted at position 2 by a methyl group and (also at position 2) either a saturated or a triply-unsaturated hydrocarbon chain consisting of three isoprenoid units. The major function of vitamin E is to act as a natural antioxidant by scavenging free radicals and molecular oxygen. Vitamin E: A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS. | alpha-tocopherol | algal metabolite; antiatherogenic agent; anticoagulant; antioxidant; antiviral agent; EC 2.7.11.13 (protein kinase C) inhibitor; immunomodulator; micronutrient; nutraceutical; plant metabolite |
| phenethyl isothiocyanate | phenethyl isothiocyanate : An isothiocyanate having a phenethyl group attached to the nitrogen. It is a naturally occurring compound found in some cruciferous vegetables (e.g. watercress) and is known to possess anticancer properties. phenethyl isothiocyanate: a dietary liver aldehyde dehydrogenase inhibitor; promotes urinary bladder carcinoma | isothiocyanate | antineoplastic agent; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; metabolite |
| cannabichromene | 1-benzopyran | ||
| allicin | botanical anti-fungal agent; sulfoxide | antibacterial agent | |
| voacamine | alkaloid ester; methyl ester; monoterpenoid indole alkaloid; organic heteropentacyclic compound; tertiary amino compound | angiogenesis inhibitor; antineoplastic agent; plant metabolite | |
| (6ar-trans)-isomer of tetrahydrocannabivarin 9 | |||
| cp-55,940 | |||
| 1,1'-biphenyl-4-yl-boronic acid | |||
| 4-hydroxybenzyl isothiocyanate | 4-hydroxybenzyl isothiocyanate: found in white mustard; structure in first source | phenols | |
| Tetrahydropiperine | benzodioxoles | ||
| geraniol | 3,7-dimethylocta-2,6-dien-1-ol; monoterpenoid; primary alcohol | allergen; fragrance; plant metabolite; volatile oil component | |
| piperine | piperine : A N-acylpiperidine that is piperidine substituted by a (1E,3E)-1-(1,3-benzodioxol-5-yl)-5-oxopenta-1,3-dien-5-yl group at the nitrogen atom. It is an alkaloid isolated from the plant Piper nigrum. | benzodioxoles; N-acylpiperidine; piperidine alkaloid; tertiary carboxamide | food component; human blood serum metabolite; NF-kappaB inhibitor; plant metabolite |
| ilepcimide | ilepcimide: structure given in first source; RN given refers to compound with no isomeric designation | benzodioxoles | |
| nerol | nerol : The (2Z)-stereoisomer of 3,7-dimethylocta-2,6-dien-1-ol. It has been isolated from the essential oils from plants like lemon grass. | 3,7-dimethylocta-2,6-dien-1-ol | fragrance; plant metabolite; volatile oil component |
| cannabidiol | cannabidiol : An cannabinoid that is cyclohexene which is substituted by a methyl group at position 1, a 2,6-dihydroxy-4-pentylphenyl group at position 3, and a prop-1-en-2-yl group at position 4. Cannabidiol: Compound isolated from Cannabis sativa extract. | olefinic compound; phytocannabinoid; resorcinols | antimicrobial agent; plant metabolite |
| sb 366791 | N-(3-methoxyphenyl)-4-chlorocinnamanilide: a TRPV1 antagonist; structure in first source | ||
| (e)-3-(4-t-butylphenyl)-n-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide | 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide: a vanilloid receptor 1 antagonist and antihyperalgesic agent; structure in first source | ||
| hc 030031 | 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide: a TRPA1 channel blocker | ||
| zucapsaicin | methoxybenzenes; phenols | ||
| capsaicin | ALGRX-4975: an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief capsaicinoid : A family of aromatic fatty amides produced as secondary metabolites by chilli peppers. | capsaicinoid | non-narcotic analgesic; TRPV1 agonist; voltage-gated sodium channel blocker |
| geranyl acetate | geranyl acetate : A monoterpenoid that is the acetate ester derivative of geraniol. geranyl acetate: constituted about 90% of the palmarosa oil | acetate ester; monoterpenoid | plant metabolite |
| capsazepine | capsazepine : A benzazepine that is 2,3,4,5-tetrahydro-1H-2-benzazepine which is substituted by hydroxy groups at positions 7 and 8 and on the nitrogen atom by a 2-(p-chlorophenyl)ethylaminothiocarbonyl group. A synthetic analogue of capsaicin, it was the first reported capsaicin receptor antagonist. capsazepine: modified capsaicin molecule; a capsaicin receptor antagonist | benzazepine; catechols; monochlorobenzenes; thioureas | capsaicin receptor antagonist |
| phorbol 12-phenylacetate 13-acetate 20-homovanillate | phorbol 12-phenylacetate 13-acetate 20-homovanillate: behavior contrasts with resiniferatoxin and capsaicin in the lack of cooperativity in binding vanilloid (capsaicin) receptor | ||
| 6-iodonordihydrocapsaicin | 6-iodonordihydrocapsaicin: a TRPV1 antagonist | methoxybenzenes; phenols | |
| pinosylvin | pinosylvin: phytoalexin found in pine and eucalyptus | pinosylvin | |
| Pinosylvin methyl ether | stilbenoid | ||
| pterostilbene | diether; methoxybenzenes; stilbenol | anti-inflammatory agent; antineoplastic agent; antioxidant; apoptosis inducer; hypoglycemic agent; neuroprotective agent; neurotransmitter; plant metabolite; radical scavenger | |
| shogaol | shogaol: from ginger, ZINGIBER OFFICINALE; less mutagenic than GINGEROL; structure given in first source | enone; monomethoxybenzene; phenols | |
| anandamide | anandamide : An N-acylethanolamine 20:4 resulting from the formal condensation of carboxy group of arachidonic acid with the amino group of ethanolamine. | endocannabinoid; N-acylethanolamine 20:4 | human blood serum metabolite; neurotransmitter; vasodilator agent |
| arachidonyl dopamine | arachidonyl dopamine: a ligand for the vanilloid receptor VR1 | catechols; fatty amide; N-(fatty acyl)-dopamine; secondary carboxamide | |
| 4,4'-dihydroxystilbene | stilbene-4,4'-diol | ||
| linoleoyl ethanolamide | linoleoyl ethanolamide : An N-acylethanolamine 18:2 that is the ethanolamide of linoleic acid. linoleoyl ethanolamide: RN given for (Z,Z)-isomer | N-acylethanolamine 18:2 | EC 3.5.1.99 (fatty acid amide hydrolase) inhibitor |
| n-oleoylethanolamine | N-oleoylethanolamine: ceramidase inhibitor oleoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of oleic acid. The monounsaturated analogue of the endocannabinoid anandamide. | endocannabinoid; N-(long-chain-acyl)ethanolamine; N-acylethanolamine 18:1 | EC 3.5.1.23 (ceramidase) inhibitor; geroprotector; PPARalpha agonist |
| 4-hydroxystilbene | 4-hydroxystilbene: RN given refers to cpd without isomeric designation stilben-4-ol : A phenol having the structure of stilbene with a hydroxy function at C-4 of one of the phenyl rings; the stereochemistry across the alkene bond is not specified. | stilben-4-ol | |
| olvanil | methoxybenzenes; phenols | ||
| cannabigerol | cannabigerol : A member of the class of resorcinols that is resorcinol which is substituted by a (2E)-3,7-dimethylocta-2,6-dien-1-yl group at position 2 and by a pentyl group at position 5. It is a natural product found in Cannabis sativa and Helichrysum species. cannabigerol: RN given refers to (E)-isomer; structure given in first source | phytocannabinoid; resorcinols | anti-inflammatory agent; antibacterial agent; antioxidant; appetite enhancer; cannabinoid receptor agonist; neuroprotective agent; plant metabolite |
| 3,5-dimethoxy-trans-stilbene | 3,5-dimethoxystilbene: structure in first source | stilbenoid | |
| albaconol | albaconol: from the mushroom Albatrellus; structure in first source | ||
| Piperanine | benzodioxoles | ||
| piperlonguminine | piperlonguminine: from Piper longum; structure in first source | benzodioxoles | |
| 3,4',5-trimethoxystilbene | 3,4',5-trimethoxystilbene: structure in first source | ||
| catharanthine | alkaloid ester; bridged compound; methyl ester; monoterpenoid indole alkaloid; organic heteropentacyclic compound; tertiary amino compound | ||
| iodoresiniferatoxin | iodoresiniferatoxin: a vanilloid receptor 1 antagonist | ||
| arvanil | arvanil: structure in first source | methoxybenzenes; phenols | |
| am 404 | anilide | ||
| 1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea | 1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea: structure in first source | ||
| sb 705498 | SB 705498: structure in first source | ||
| n-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2h)-carboxamide | N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide: a vanilloid receptor 1 antagonist and analgesic; structure in first source | piperazines; pyridines | |
| arachidonoylserotonin | arachidonoylserotonin: an NSAID with antinociceptive activity; fatty acid amide hydrolase inhibitor; structure in first source N-arachidonoylserotonin : An N-acylserotonin obtained by formal condensation of the carboxy group of arachidonic acid with the primary amino group of serotonin. | N-acylserotonin; phenols | anti-inflammatory agent; anticonvulsant; antioxidant; capsaicin receptor antagonist; EC 3.5.1.99 (fatty acid amide hydrolase) inhibitor; human metabolite; signalling molecule |
| jyl 1421 | JYL 1421: a vanilloid receptor antagonist; structure in first source | ||
| abt 102 | ABT 102: a TRPV1 antagonist; structure in first source | ||
| jnj 17203212 | |||
| a 784168 | 1-(3-(trifluoromethyl)pyridin-2-yl)-N-(4-(trifluoromethylsulfonyl)phenyl)-1,2,3,6-tetrahydropyridine-4-carboxamide: a TRPV1 antagonist | ||
| ly2183240 | LY2183240: structure in first source | biphenyls | |
| methylphenidate | N-phenyl-4-(quinolin-2-ylmethyl)piperazine-1-carboxamide: a fatty acid amide hydrolase inhibitor; structure in first source | ||
| cannabidivarin | cannabidivarin: from Cannabis sativa | monoterpenoid | |
| amg 517 | |||
| a 803467 | A 803467: an Nav1.8 sodium channel blocker; structure in first source | ||
| mavatrep | mavatrep: a transient receptor potential vanilloid 1 antagonist; structure in first source | ||
| am 6701 | |||
| voacristine | voacristine: indole alkaloid from leaves of Ervatamia coronaria; RN given for 20(S)-isomer; structure given in first source | ||
| abt 116 | ABT 116: a TRPV1 antagonist with analgesic activity; structure in first source |