ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated.
If you have any questions, please contact Marianne Reed at mreed@ku.edu .
Human apolipoprotein E isoforms are differentially sialylated and the sialic acid moiety in ApoE2 attenuates ApoE2-Aβ interaction and Aβ fibrillation
dc.contributor.author | Moon, Hee-Jung | |
dc.contributor.author | Haroutunian, Vahram | |
dc.contributor.author | Zhao, Liqin | |
dc.date.accessioned | 2023-03-10T15:13:22Z | |
dc.date.available | 2023-03-10T15:13:22Z | |
dc.date.issued | 2022-01-15 | |
dc.identifier.citation | Moon, H. J., Haroutunian, V., & Zhao, L. (2022). Human apolipoprotein E isoforms are differentially sialylated and the sialic acid moiety in ApoE2 attenuates ApoE2-Aβ interaction and Aβ fibrillation. Neurobiology of disease, 164, 105631. https://doi.org/10.1016/j.nbd.2022.105631 | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/34034 | |
dc.description.abstract | The APOE genotype is the most prominent genetic risk factor for the development of late-onset Alzheimer’'s disease (LOAD); however, the underlying mechanisms remain unclear. In the present study, we found that the sialylation profiles of ApoE protein in the human brain are significantly different among the three isoforms, with ApoE2 exhibiting the most abundant sialic acid modification whereas ApoE4 had the least. We further observed that the sialic acid moiety in ApoE2 significantly affected the interaction between ApoE2 and Aβ peptides. The removal of sialic acid in ApoE2 increased the ApoE2 binding affinity for the Aβ17–24 region of Aβ and promoted Aβ fibrillation. These findings provide a plausible explanation for the well-documented differential roles of ApoE isoforms in Aβ pathogenesis. Specifically, compared to the other two isotypes, the higher expression of sialic acid in ApoE2 may contribute to the less potent interaction between ApoE2 and Aβ and ultimately the slower rate of brain Aβ deposition, a mechanism thought to underlie ApoE2-mediated decreased risk for AD. Future studies are warranted to determine whether the differential sialylation in ApoE isoforms may also contribute to some of their other distinct properties, such as their divergent preferences in associations with lipids and lipoproteins, as well as their potential impact on neuroinflammation through modulation of microglial Siglec activity. Overall, our findings lead to the insight that the sialic acid structure is an important posttranslational modification (PTM) that alters ApoE protein functions with relevance for AD. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | en_US |
dc.subject | Late-onset Alzheimer's disease (LOAD) | en_US |
dc.subject | Apolipoprotein E (ApoE) | en_US |
dc.subject | Amyloid-β (Aβ) | en_US |
dc.subject | ApoE-Aβ interaction | en_US |
dc.subject | Sialic acid | en_US |
dc.subject | Sialylation | en_US |
dc.title | Human apolipoprotein E isoforms are differentially sialylated and the sialic acid moiety in ApoE2 attenuates ApoE2-Aβ interaction and Aβ fibrillation | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Moon, Hee-Jung | |
kusw.kuauthor | Zhao, Liqin | |
kusw.kudepartment | Pharmacology and Toxicology | en_US |
kusw.kudepartment | Neuroscience Graduate Program | en_US |
dc.identifier.doi | 10.1016/j.nbd.2022.105631 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC9809161 | en_US |
dc.rights.accessrights | openAccess | en_US |
Files in this item
This item appears in the following Collection(s)
-
Pharmacy Scholarly Works [299]