Přehled o publikaci
2023
Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
NEMERGUT, Michal; Sérgio Manuel MARQUES; Lukáš UHRÍK; Tereza VÁŇOVÁ; Markéta NEZVEDOVÁ et. al.Basic information
Original name
Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
Authors
NEMERGUT, Michal (703 Slovakia, belonging to the institution); Sérgio Manuel MARQUES (620 Portugal, belonging to the institution); Lukáš UHRÍK (703 Slovakia); Tereza VÁŇOVÁ (203 Czech Republic, belonging to the institution); Markéta NEZVEDOVÁ (203 Czech Republic, belonging to the institution); Darshak Chandulal GADARA (356 India, belonging to the institution); Durga JHA (356 India, belonging to the institution); Jan TULIS (203 Czech Republic, belonging to the institution); Veronika NOVÁKOVÁ (203 Czech Republic, belonging to the institution); Joan PLANAS IGLESIAS (724 Spain, belonging to the institution); Antonín KUNKA (203 Czech Republic, belonging to the institution); Anthony Thomas P LEGRAND (250 France, belonging to the institution); Hana HŘÍBKOVÁ (203 Czech Republic, belonging to the institution); Veronika POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution); Jiří SEDMÍK (203 Czech Republic, belonging to the institution); Jan RAŠKA (203 Czech Republic, belonging to the institution); Zbyněk PROKOP (203 Czech Republic, belonging to the institution); Jiří DAMBORSKÝ (203 Czech Republic, guarantor, belonging to the institution); Dáša BOHAČIAKOVÁ (703 Slovakia, belonging to the institution); Zdeněk SPÁČIL (203 Czech Republic, belonging to the institution); Lenka HERNYCHOVÁ (203 Czech Republic); David BEDNÁŘ (203 Czech Republic, belonging to the institution) and Martin MAREK (203 Czech Republic, belonging to the institution)
Edition
Molecular Neurodegeneration, England, BMC, 2023, 1750-1326
Other information
Language
English
Type of outcome
Article in a journal
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
is not subject to a state or trade secret
References:
RIV identification code
RIV/00216224:14310/23:00130923
Organization
Přírodovědecká fakulta – Repository – Repository
UT WoS
001007628800001
EID Scopus
2-s2.0-85161210803
Keywords in English
Apolipoprotein E; Alzheimer’s disease; Neurodegeneration; Aggregation; Cerebral organoids; Molecular dynamics; HDX-MS; Protein crystallography; Proteomics; Lipidomics; Tramiprosate; 3-sulfopropanoic acid
Links
EF17_043/0009632, research and development project. EF18_046/0015974, research and development project. GA21-21510S, research and development project. GA22-09853S, research and development project. LM2018131, research and development project. LM2018140, research and development project. LM2023069, research and development project. LX22NPO5107, research and development project. 101087124, interní kód Repo. 857560, interní kód Repo. CIISB III, large research infrastructures.
Changed: 22/2/2025 00:51, RNDr. Daniel Jakubík
Abstract
V originále
gt; 15 A) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce ApoE3-like conformational behavior in ApoE4 and reduce its aggregation propensity. Analysis of ApoE epsilon 4/epsilon 4 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage products of excess cholesterol. Conclusions Our results connect the ApoE4 structure with its aggregation propensity, providing a new druggable target for neurodegeneration and ageing.
