J
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; Sérgio Manuel MARQUES; Lukáš UHRÍK; Tereza VÁŇOVÁ; Markéta NEZVEDOVÁ; Darshak Chandulal GADARA; Durga JHA; Jan TULIS; Veronika NOVÁKOVÁ; Joan PLANAS IGLESIAS; Antonín KUNKA; Anthony Thomas P LEGRAND; Hana HŘÍBKOVÁ; Veronika POSPÍŠILOVÁ; Jiří SEDMÍK; Jan RAŠKA; Zbyněk PROKOP; Jiří DAMBORSKÝ; Dáša BOHAČIAKOVÁ; Zdeněk SPÁČIL; Lenka HERNYCHOVÁ; David BEDNÁŘ and Martin MAREK
Edition
Molecular Neurodegeneration, England, BMC, 2023, 1750-1326
Other information
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
RIV identification code
RIV/00216224:14310/23:00130923
Organization
Přírodovědecká fakulta – Repository – Repository
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.
In the original language
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.
Displayed: 16/12/2025 15:12