Synergistic effects of mutation and glycosylation on disease progression
Glycosylation, a post-translational modification, plays a crucial role in proper localization and function of proteins. It is regulated by multiple glycosyltransferases and can be influenced by various factors. Inherited missense mutations in glycosylated proteins such as NOTCH3, Low-density lipopro...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1550815/full |
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| author | Shodai Suzuki Motoyuki Itoh Motoyuki Itoh Motoyuki Itoh |
| author_facet | Shodai Suzuki Motoyuki Itoh Motoyuki Itoh Motoyuki Itoh |
| author_sort | Shodai Suzuki |
| collection | DOAJ |
| description | Glycosylation, a post-translational modification, plays a crucial role in proper localization and function of proteins. It is regulated by multiple glycosyltransferases and can be influenced by various factors. Inherited missense mutations in glycosylated proteins such as NOTCH3, Low-density lipoprotein receptor (LDLR), and Amyloid precursor protein (APP) could affect their glycosylation states, leading to cerebral small vessel disease, hypercholesterolemia, and Alzheimer’s disease, respectively. Additionally, physiological states and aging-related conditions can affect the expression levels of glycosyltransferases. However, the interplay between mutations in glycosylated proteins and changes in their glycosylation levels remains poorly understood. This mini-review summarizes the effects of glycosylation on transmembrane proteins with pathogenic mutations, including NOTCH3, LDLR, and APP. We highlight the synergistic contributions of missense amino acids in the mutant proteins and alterations in their glycosylation states to their molecular pathogenesis. |
| format | Article |
| id | doaj-art-c0fe7c6de34947879d48ba4de937d16a |
| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-c0fe7c6de34947879d48ba4de937d16a2025-02-04T05:28:13ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-02-011210.3389/fmolb.2025.15508151550815Synergistic effects of mutation and glycosylation on disease progressionShodai Suzuki0Motoyuki Itoh1Motoyuki Itoh2Motoyuki Itoh3Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, JapanDepartment of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, JapanResearch Institute of Disaster Medicine, Chiba University, Chiba, JapanHealth and Disease Omics Center, Chiba University, Chiba, JapanGlycosylation, a post-translational modification, plays a crucial role in proper localization and function of proteins. It is regulated by multiple glycosyltransferases and can be influenced by various factors. Inherited missense mutations in glycosylated proteins such as NOTCH3, Low-density lipoprotein receptor (LDLR), and Amyloid precursor protein (APP) could affect their glycosylation states, leading to cerebral small vessel disease, hypercholesterolemia, and Alzheimer’s disease, respectively. Additionally, physiological states and aging-related conditions can affect the expression levels of glycosyltransferases. However, the interplay between mutations in glycosylated proteins and changes in their glycosylation levels remains poorly understood. This mini-review summarizes the effects of glycosylation on transmembrane proteins with pathogenic mutations, including NOTCH3, LDLR, and APP. We highlight the synergistic contributions of missense amino acids in the mutant proteins and alterations in their glycosylation states to their molecular pathogenesis.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1550815/fullglycosylationmutationagingNotch3LDLRAPP |
| spellingShingle | Shodai Suzuki Motoyuki Itoh Motoyuki Itoh Motoyuki Itoh Synergistic effects of mutation and glycosylation on disease progression Frontiers in Molecular Biosciences glycosylation mutation aging Notch3 LDLR APP |
| title | Synergistic effects of mutation and glycosylation on disease progression |
| title_full | Synergistic effects of mutation and glycosylation on disease progression |
| title_fullStr | Synergistic effects of mutation and glycosylation on disease progression |
| title_full_unstemmed | Synergistic effects of mutation and glycosylation on disease progression |
| title_short | Synergistic effects of mutation and glycosylation on disease progression |
| title_sort | synergistic effects of mutation and glycosylation on disease progression |
| topic | glycosylation mutation aging Notch3 LDLR APP |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1550815/full |
| work_keys_str_mv | AT shodaisuzuki synergisticeffectsofmutationandglycosylationondiseaseprogression AT motoyukiitoh synergisticeffectsofmutationandglycosylationondiseaseprogression AT motoyukiitoh synergisticeffectsofmutationandglycosylationondiseaseprogression AT motoyukiitoh synergisticeffectsofmutationandglycosylationondiseaseprogression |