Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum
Hereditary transthyretin amyloidosis (ATTRv) results from genetic mutations that destabilize transthyretin (TTR), leading to the formation of extracellular aggregates and amyloid fibrils. A common pathological feature of ATTRv is the capacity of TTR variants to evade endoplasmic reticulum quality co...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1623185/full |
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| author | Jia Meng Shan-jun Cai Shan-jun Cai Shan-jun Cai Shan-jun Cai |
| author_facet | Jia Meng Shan-jun Cai Shan-jun Cai Shan-jun Cai Shan-jun Cai |
| author_sort | Jia Meng |
| collection | DOAJ |
| description | Hereditary transthyretin amyloidosis (ATTRv) results from genetic mutations that destabilize transthyretin (TTR), leading to the formation of extracellular aggregates and amyloid fibrils. A common pathological feature of ATTRv is the capacity of TTR variants to evade endoplasmic reticulum quality control (ERQC) and be secreted, underscoring the critical role of ER regulation in disease pathogenesis. Notably, the TTR Gly83Arg mutation causes familial vitreous amyloidosis, a subtype distinguished by abnormal TTR deposition in the ocular vitreous cavity. Current therapies for ATTRv are ineffective in crossing the blood-retinal barrier or in halting the progression of ocular amyloidosis. This review summarizes the molecular mechanisms of ER-regulated TTR secretion and explores potential causes of ocular amyloid deposition, aiming to provide mechanistic insights into familial vitreous amyloidosis. |
| format | Article |
| id | doaj-art-548644edc8d8454fb7ea2d40eab4d8eb |
| institution | DOAJ |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-548644edc8d8454fb7ea2d40eab4d8eb2025-08-20T03:15:54ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-07-011610.3389/fphys.2025.16231851623185Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulumJia Meng0Shan-jun Cai1Shan-jun Cai2Shan-jun Cai3Shan-jun Cai4Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaGuizhou Eye Hospital, Zunyi, ChinaGuizhou Branch of National Eye Disease Clinical Research Center, Zunyi, ChinaSpecial Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi, ChinaHereditary transthyretin amyloidosis (ATTRv) results from genetic mutations that destabilize transthyretin (TTR), leading to the formation of extracellular aggregates and amyloid fibrils. A common pathological feature of ATTRv is the capacity of TTR variants to evade endoplasmic reticulum quality control (ERQC) and be secreted, underscoring the critical role of ER regulation in disease pathogenesis. Notably, the TTR Gly83Arg mutation causes familial vitreous amyloidosis, a subtype distinguished by abnormal TTR deposition in the ocular vitreous cavity. Current therapies for ATTRv are ineffective in crossing the blood-retinal barrier or in halting the progression of ocular amyloidosis. This review summarizes the molecular mechanisms of ER-regulated TTR secretion and explores potential causes of ocular amyloid deposition, aiming to provide mechanistic insights into familial vitreous amyloidosis.https://www.frontiersin.org/articles/10.3389/fphys.2025.1623185/fullendoplasmic reticulumendoplasmic reticulum quality controlunfolded protein responsetransthyretinvitreous amyloidosis |
| spellingShingle | Jia Meng Shan-jun Cai Shan-jun Cai Shan-jun Cai Shan-jun Cai Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum Frontiers in Physiology endoplasmic reticulum endoplasmic reticulum quality control unfolded protein response transthyretin vitreous amyloidosis |
| title | Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum |
| title_full | Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum |
| title_fullStr | Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum |
| title_full_unstemmed | Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum |
| title_short | Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum |
| title_sort | secretion of transthyretin molecular mechanisms dependent on the endoplasmic reticulum |
| topic | endoplasmic reticulum endoplasmic reticulum quality control unfolded protein response transthyretin vitreous amyloidosis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1623185/full |
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