http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-3338787-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_050fc7b82c5d17d9aeb63a7cdcc546b3 http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_0624908c7150e45bdd907be4f162057e |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/Y02A50-30 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-13 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-122 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-138 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K38-05 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K38-16 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K38-10 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K38-1709 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P25-28 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K38-05 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K38-10 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K38-16 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-13 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-122 |
| filingDate | 2016-07-15-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0f5dcd58063cc641a74b1f7d0af8126a http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_562c0a449685995d86250bdd76be3477 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_1ef2ce1a24392f21bee00d4f6c7da209 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a3b598d43c4169f27122cca8c2dcac40 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_cd877ee886cbd67f4b18d92c8d74ee70 |
| publicationDate | 2018-06-27-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | EP-3338787-A1 |
| titleOfInvention | Prevention and treatment of neurodegenerative diseases through autophagy activity mediated by ligand or arginylated bip binding to p62 zz domain |
| abstract | The pharmacokinetics and key technologies of the present invention are summarized in Figure 1 . Particularly, malignant misfolded proteins such as mutant huntingtin and alpha-synuclein are coagulated and grow into oligomeric coagulum ( , ¡), fibrillar coagulum (¢) and eventually inclusion body (£). Young neurons produce a large amount of Nt-Arg through N-terminal arginylation (¤) of vesicle chaperones such as BiP secreted into the cytoplasm, and then arginylated BiP (R-BiP) is secreted binds to the misfolded proteins (¥). As a ligand, the Nt-Arg of R-BiP binds to the p62 ZZ domain (¦), and the normally inactivated closed form of p62 is changed to an open form, leading to structural activation (§). As a result, PB1 and LC3-binding domains are exposed. The PB1 domain induces oligomerization (¨), leading to the concentration as a p62 body (©) that is a coagulum capable of being degraded by autophagy. Then, p62 binds to LC3, which is protruding from the autopagosomal membranes, leading to the completion of autophagy targeting (ª) and lysosomal proteolysis. Since autophagy proteolysis including steps ¤-ª is strong in young neurons, cytotoxic protein coagulums ( -¤) do not accumulate. However in aged neurons, autophagy proteolysis including steps ¤-ª is weakened, and protein coagulums ( -¤) accumulate and become cytotoxic. In this invention, p62 is intentionally activated («, ¬) by using low mass ligands of the p62 ZZ domain to effectively remove huntingtin and alpha-synuclein protein coagulums. Particularly, in step «, p62 ligated with a ligand accelerates the oligomerization of p62-R-BiP-misfolded protein (¨) and the formation of autophagy coagulum (©). In step ¬, the ligand-p62 conjugate acts as an autophagy activator () to induce the synthesis of LC3 and the conversion of LC3-I into LC3-II in order to accelerate the formation of autophagosomes (®). |
| isCitedBy | http://rdf.ncbi.nlm.nih.gov/pubchem/patent/JP-2022511234-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/WO-2019239126-A1 http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-3988090-A4 |
| priorityDate | 2015-08-18-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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