Page last updated: 2024-10-24

positive regulation of amyloid precursor protein biosynthetic process

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of amyloid precursor protein (APP), the precursor of amyloid-beta. [GOC:go_curators]

Positive regulation of amyloid precursor protein biosynthetic process refers to the mechanisms that enhance or stimulate the production and maturation of amyloid precursor protein (APP). APP is a transmembrane protein that undergoes complex processing within the cell, leading to the formation of amyloid-beta (Aβ) peptides.

APP biosynthesis begins with the transcription and translation of the APP gene, resulting in the production of a precursor protein. This precursor undergoes several modifications, including glycosylation and proteolytic cleavage by enzymes called secretases.

The key secretases involved in APP processing are β-secretase (BACE1) and γ-secretase. BACE1 cleaves APP within its ectodomain, generating an N-terminal fragment called sAPPα and a C-terminal fragment called C99. C99 is further cleaved by γ-secretase, which can release either Aβ peptides or a soluble APP fragment called AICD.

Positive regulation of APP biosynthesis can occur at multiple levels, including:

- Transcriptional regulation of the APP gene: Various factors can enhance the transcription of the APP gene, leading to increased production of APP mRNA and ultimately, APP protein.
- Post-translational modifications: Modifications such as glycosylation can influence APP stability and processing.
- Secretases activity: Regulation of BACE1 and γ-secretase activity can impact APP processing and Aβ production.

Disregulation of APP biosynthesis and processing is implicated in Alzheimer's disease, a neurodegenerative disorder characterized by the accumulation of Aβ plaques in the brain. Therefore, understanding the mechanisms involved in the positive regulation of APP biosynthetic process is crucial for developing therapeutic strategies to target Aβ production and potentially alleviate Alzheimer's disease pathology.'
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Proteins (2)

ProteinDefinitionTaxonomy
NicastrinA nicastrin that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92542]Homo sapiens (human)
Sterol O-acyltransferase 1A sterol O-acyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35610]Homo sapiens (human)

Compounds (51)

CompoundDefinitionClassesRoles
diethyl pyrocarbonatediethyl pyrocarbonate : The diethyl ester of dicarbonic acid.

Diethyl Pyrocarbonate: Preservative for wines, soft drinks, and fruit juices and a gentle esterifying agent.
acyclic carboxylic anhydride
7-amino-4-chloro-3-methoxy-2-benzopyran-1-oneisocoumarins
procainamideprocainamide : A benzamide that is 4-aminobenzamide substituted on the amide N by a 2-(diethylamino)ethyl group. It is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias.

Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.
benzamidesanti-arrhythmia drug;
platelet aggregation inhibitor;
sodium channel blocker
edrophonium chlorideedrophonium chloride : The chloride salt of edrophonium. A reversible inhibitor of cholinesterase with a rapid onset (30-60 seconds after injection) but a short duration of action (5-15 minutes), it is used in myasthenia gravis both diagnostically and to distinguish between under- or over-treatment with other anticholinesterases. It has also been used for the reversal of neuromuscular blockade in anaesthesia, and for the management of poisoning due to tetrodotoxin, a neuromuscular blocking toxin found in puffer fish and other marine animals.chloride salt;
quaternary ammonium salt
antidote;
diagnostic agent;
EC 3.1.1.8 (cholinesterase) inhibitor
tarenflurbiltarenflurbil: R-enantiomer of flurbiprofen but not a COX inhibitor; modulates NF-kB, gamma-secretase, amyloid beta-protein;flurbiprofen
cholanic acid5beta-cholanic acids;
cholanic acid
territrem bterritrem B: tremorgenic mycotoxin from Aspergillus terreus; RN given refers to (4aR-(4aalpha,6abeta,12aalpha,12bbeta))-isomer
pd 128042PD 128042: structure given in first sourceanilide
cl 277082CL 277082: structure given in first source
1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone: an inhibitor of cholesterol absorption; structure given in first source
atractylenolide iiiatractylenolide III: from Atractylodes macrocephala Koidz; structure in first sourcenaphthofuranmetabolite
avasimibemonoterpenoid
22s-hydroxycholesterol(22S)-22-hydroxycholesterol : An oxysterol that is the 22S-hydroxy derivative of cholesterol.22-hydroxy steroid;
3beta-hydroxy-Delta(5)-steroid;
oxysterol
f 1394F 1394: an acyl-CoA:cholesterol acyltransferase (ACAT) inibitor; structure given in first source
oleic acidoleic acid : An octadec-9-enoic acid in which the double bond at C-9 has Z (cis) stereochemistry.

Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)
octadec-9-enoic acidantioxidant;
Daphnia galeata metabolite;
EC 3.1.1.1 (carboxylesterase) inhibitor;
Escherichia coli metabolite;
mouse metabolite;
plant metabolite;
solvent
t0901317T0901317: an LXRalpha and LXRbeta agonist
beta-hydroxyisovalerylshikonin
shikoninshikonin: a naphthazarin; has antineoplastic and angiogenesis inhibiting activitieshydroxy-1,4-naphthoquinone
carbenoxolone
pactimibe
linoleic acidlinoleic acid : An octadecadienoic acid in which the two double bonds are at positions 9 and 12 and have Z (cis) stereochemistry.

Linoleic Acid: A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)
octadecadienoic acid;
omega-6 fatty acid
algal metabolite;
Daphnia galeata metabolite;
plant metabolite
oleylamidealiphatic amide : A carboxamide in which the amide linkage is bonded directly to an aliphatic system.

oleamide : A fatty amide derived from oleic acid.

oleylamide: plastic additive; can cause contact urticaria; RN given refers to (Z)-isomer; a sleep inducing factor
primary fatty amidehuman metabolite;
plant metabolite
n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl esterDAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor.carboxylic ester;
difluorobenzene;
dipeptide;
tert-butyl ester
EC 3.4.23.46 (memapsin 2) inhibitor
sulindac sulfidesulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity.

sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source
aryl sulfide;
monocarboxylic acid;
organofluorine compound
antineoplastic agent;
apoptosis inducer;
non-steroidal anti-inflammatory drug
macluraxanthone bmacluraxanthone B : A member of the class of xanthones that is 9H-xanthen-9-one substituted by hydroxy groups at positions 1, 3, 6 and 7, a dimethylallyl group at position 2 and a prenyl group at position 4. Isolated from Maclura tinctoria and Cudrania tricuspidata, it exhibits anti-HIV and antineoplastic activity.

macluraxanthone B: from the plant Maclura tinctoria; structure in first source
phenols;
xanthones
anti-HIV agent;
antineoplastic agent;
metabolite
oleoylanilideoleoylanilide: alters lipid metabolism of lung & adipose tissue; do not confuse with oleoanilide; RN given refers to (Z)-isomer

oleylanilide : The fatty amide resulting from the formal condensation of oleic acid and aniline.
anilide;
fatty amide
Pipercidebenzodioxoles
l 685458L 685458: a gamma-secretase inhibitor; structure in first source

L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease.
carbamate ester;
monocarboxylic acid amide;
peptide;
secondary alcohol
EC 3.4.23.46 (memapsin 2) inhibitor;
peptidomimetic
linoleamidelinoleamide : A fatty amide obtained from linoleic acid.

linoleamide: C18-H33-N-O
primary fatty amidehuman metabolite
manzamine amanzamine A : An alkaloid of the class of beta-carbolines isolated from Haliclona and Acanthostrongylophora. It exhibits inhibitory activity against Glycogen Synthase Kinase-3 (EC 2.7.11.26).

manzamine A: RN given refers to (1R-(1R*,9Z,13S*,13aR*,20aR*,21aR*)-isomer; RN for cpd without isomeric designation not avail 12/92
alkaloid;
beta-carbolines;
isoquinolines
animal metabolite;
anti-HSV-1 agent;
antimalarial;
antineoplastic agent;
EC 2.7.11.26 (tau-protein kinase) inhibitor;
marine metabolite
mk 0752
eflucimibeeflucimibe: a powerful and systemic acylcoenzyme A: cholesterol acyltransferase inhibitor
ly 450139peptide
chf 50741-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid: a beta-amyloid(1-42) lowering agent; structure in first source
arisugacinarisugacin A : An organic heterotetracyclic compound that is 4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-4a,6,6a,12,12a,12b-hexahydro-4H,11H-benzo[f]pyrano[4,3-b]chromene-1,11(5H)-dione substituted by 3,4-dimethoxyphenyl group at position 9 (the 4aR,6aR,12aS,12bS steroisomer). Isolated from the culture broth of Penicillium, it acts as a selective inhibitor of acetylcholinesterase.

arisugacin: isolated from Penicillium sp. FO-4259; structure given in first source
aromatic ether;
delta-lactone;
enone;
organic heterotetracyclic compound;
tertiary alcohol
antimicrobial agent;
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
metabolite;
Penicillium metabolite
ly 411575dibenzoazepine;
difluorobenzene;
lactam;
secondary alcohol
EC 3.4.23.46 (memapsin 2) inhibitor
manassantin bmanassantin B : A lignan isolated from Saururus cernuus and Saururus chinensis and has been shown to exhibit antineoplastic activity.

manassantin B: isolated from the roots of Saururus chinensis; structure in first source
benzodioxoles;
dimethoxybenzene;
lignan;
oxolanes;
secondary alcohol
antineoplastic agent;
metabolite
4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acidsulfonamide
begacestat
cudraxanthone lcudraxanthone L: from the root bark of Cudrania tricuspidata; structure in first source
e 2012
mrk 560MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source
cudraflavanone acudraflavanone A: antineoplastic from Cudrania tricuspidata; structure in first source
azd7687AZD7687: structure in first source
manassantin amanassantin A : A lignan isolated from Saururus cernuus and Saururus chinensis and has been shown to exhibit antineoplastic activity.

manassantin A: a dineolignan from Saururus cernuus; structure in first source
1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone: structure in first source
pf 3084014nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment.

nirogacestat: an antineoplastic agent
bms 708163BMS 708163: structure in first sourceoxadiazole;
ring assembly
ro 4929097dibenzoazepine;
dicarboxylic acid diamide;
lactam;
organofluorine compound
EC 3.4.23.46 (memapsin 2) inhibitor
jnj 40418677
(r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline(R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline: gamma secretase inhibitor; structure in first source