Domino-like effect of C112R mutation on ApoE4 aggregation and
its reduction by Alzheimer’s Disease drug candidate

CSLog in Log in (EduId)

Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease ...

Přehled o publikaci

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

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:

URL

RIV identification code

RIV/00216224:14310/23:00130923

Organization

Přírodovědecká fakulta – Repository – Repository

DOI

https://doi.org/10.1186/s13024-023-00620-9

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

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.

Files attached

https://is.muni.cz/publication/2289318/2289318.pdf

Cite

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. Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate. Molecular Neurodegeneration. England: BMC, 2023, vol. 18, No 1, p. 1-25. ISSN 1750-1326. Available from: https://doi.org/10.1186/s13024-023-00620-9.

@article{57066,
   author = {Nemergut, Michal and Marques, Sérgio Manuel and Uhrík, Lukáš and Váňová, Tereza and Nezvedová, Markéta and Gadara, Darshak Chandulal and Jha, Durga and Tulis, Jan and Nováková, Veronika and Planas Iglesias, Joan and Kunka, Antonín and Legrand, Anthony Thomas P and Hříbková, Hana and Pospíšilová, Veronika and Sedmík, Jiří and Raška, Jan and Prokop, Zbyněk and Damborský, Jiří and Bohačiaková, Dáša and Spáčil, Zdeněk and Hernychová, Lenka and Bednář, David and Marek, Martin},
   article_location = {England},
   article_number = {1},
   doi = {https://doi.org/10.1186/s13024-023-00620-9},
   keywords = {Apolipoprotein E; Alzheimer’s disease; Neurodegeneration; Aggregation; Cerebral organoids; Molecular dynamics; HDX-MS; Protein crystallography; Proteomics; Lipidomics; Tramiprosate; 3-sulfopropanoic acid},
   language = {eng},
   issn = {1750-1326},
   journal = {Molecular Neurodegeneration},
   title = {Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate},
   url = {https://doi.org/10.1186/s13024-023-00620-9},
   volume = {18},
   year = {2023}
}

TY  - JOUR
ID  - 57066
AU  - Nemergut, Michal - Marques, Sérgio Manuel - Uhrík, Lukáš - Váňová, Tereza - Nezvedová, Markéta - Gadara, Darshak Chandulal - Jha, Durga - Tulis, Jan - Nováková, Veronika - Planas Iglesias, Joan - Kunka, Antonín - Legrand, Anthony Thomas P - Hříbková, Hana - Pospíšilová, Veronika - Sedmík, Jiří - Raška, Jan - Prokop, Zbyněk - Damborský, Jiří - Bohačiaková, Dáša - Spáčil, Zdeněk - Hernychová, Lenka - Bednář, David - Marek, Martin
PY  - 2023
TI  - Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
JF  - Molecular Neurodegeneration
VL  - 18
IS  - 1
SP  - 1-25
EP  - 1-25
PB  - BMC
SN  - 1750-1326
KW  - Apolipoprotein E
KW  - Alzheimer’s disease
KW  - Neurodegeneration
KW  - Aggregation
KW  - Cerebral organoids
KW  - Molecular dynamics
KW  - HDX-MS
KW  - Protein crystallography
KW  - Proteomics
KW  - Lipidomics
KW  - Tramiprosate
KW  - 3-sulfopropanoic acid
UR  - https://doi.org/10.1186/s13024-023-00620-9
N2  - 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.
ER  -

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. Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate. \textit{Molecular Neurodegeneration}. England: BMC, 2023, vol.~18, No~1, p.~1-25. ISSN~1750-1326. Available from: https://doi.org/10.1186/s13024-023-00620-9.