Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

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Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies. / Nielsen, Nadia Sukusu; Poulsen, Ebbe Toftgaard; Lukassen, Marie V; Chao Shern, Connie; Mogensen, Emilie Hage; Weberskov, Christian E; DeDionisio, Larry; Schauser, Leif; Moore, Tara C B; Otzen, Daniel E; Hjortdal, Jesper; Enghild, Jan J.

In: Progress in Retinal and Eye Research, Vol. 77, 100843, 07.2020.

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Nielsen, Nadia Sukusu ; Poulsen, Ebbe Toftgaard ; Lukassen, Marie V ; Chao Shern, Connie ; Mogensen, Emilie Hage ; Weberskov, Christian E ; DeDionisio, Larry ; Schauser, Leif ; Moore, Tara C B ; Otzen, Daniel E ; Hjortdal, Jesper ; Enghild, Jan J. / Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies. In: Progress in Retinal and Eye Research. 2020 ; Vol. 77.

Bibtex

@article{576a837beb144f60ae13c5820163b8a8,
title = "Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies",
abstract = "Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-β-induced gene (TGFBI) are associated with amyloid and amorphous protein deposition in TGFBI-linked corneal dystrophies. We discuss the current understanding of the biochemical mechanisms of TGFBI-linked corneal dystrophies and propose that mutations leading to granular corneal dystrophy (GCD) decrease the solubility of TGFBIp and affect the interactions between TGFBIp and components of the corneal stroma, whereas mutations associated with lattice corneal dystrophy (LCD) lead to a destabilization of the protein that disrupts proteolytic turnover, especially by the serine protease HtrA1. Future research should focus on TGFBIp function in the cornea, confirmation of the biochemical mechanisms in vivo, and the development of disease models. Future therapies for TGFBI-linked corneal dystrophies might include topical agents that regulate protein aggregation or gene therapy that targets the mutant allele by CRISPR/Cas9 technology.",
author = "Nielsen, {Nadia Sukusu} and Poulsen, {Ebbe Toftgaard} and Lukassen, {Marie V} and {Chao Shern}, Connie and Mogensen, {Emilie Hage} and Weberskov, {Christian E} and Larry DeDionisio and Leif Schauser and Moore, {Tara C B} and Otzen, {Daniel E} and Jesper Hjortdal and Enghild, {Jan J}",
note = "Copyright {\textcopyright} 2020 Elsevier Ltd. All rights reserved.",
year = "2020",
month = jul,
doi = "10.1016/j.preteyeres.2020.100843",
language = "English",
volume = "77",
journal = "Progress in Retinal and Eye Research",
issn = "1350-9462",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

AU - Nielsen, Nadia Sukusu

AU - Poulsen, Ebbe Toftgaard

AU - Lukassen, Marie V

AU - Chao Shern, Connie

AU - Mogensen, Emilie Hage

AU - Weberskov, Christian E

AU - DeDionisio, Larry

AU - Schauser, Leif

AU - Moore, Tara C B

AU - Otzen, Daniel E

AU - Hjortdal, Jesper

AU - Enghild, Jan J

N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.

PY - 2020/7

Y1 - 2020/7

N2 - Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-β-induced gene (TGFBI) are associated with amyloid and amorphous protein deposition in TGFBI-linked corneal dystrophies. We discuss the current understanding of the biochemical mechanisms of TGFBI-linked corneal dystrophies and propose that mutations leading to granular corneal dystrophy (GCD) decrease the solubility of TGFBIp and affect the interactions between TGFBIp and components of the corneal stroma, whereas mutations associated with lattice corneal dystrophy (LCD) lead to a destabilization of the protein that disrupts proteolytic turnover, especially by the serine protease HtrA1. Future research should focus on TGFBIp function in the cornea, confirmation of the biochemical mechanisms in vivo, and the development of disease models. Future therapies for TGFBI-linked corneal dystrophies might include topical agents that regulate protein aggregation or gene therapy that targets the mutant allele by CRISPR/Cas9 technology.

AB - Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-β-induced gene (TGFBI) are associated with amyloid and amorphous protein deposition in TGFBI-linked corneal dystrophies. We discuss the current understanding of the biochemical mechanisms of TGFBI-linked corneal dystrophies and propose that mutations leading to granular corneal dystrophy (GCD) decrease the solubility of TGFBIp and affect the interactions between TGFBIp and components of the corneal stroma, whereas mutations associated with lattice corneal dystrophy (LCD) lead to a destabilization of the protein that disrupts proteolytic turnover, especially by the serine protease HtrA1. Future research should focus on TGFBIp function in the cornea, confirmation of the biochemical mechanisms in vivo, and the development of disease models. Future therapies for TGFBI-linked corneal dystrophies might include topical agents that regulate protein aggregation or gene therapy that targets the mutant allele by CRISPR/Cas9 technology.

U2 - 10.1016/j.preteyeres.2020.100843

DO - 10.1016/j.preteyeres.2020.100843

M3 - Review

C2 - 32004730

VL - 77

JO - Progress in Retinal and Eye Research

JF - Progress in Retinal and Eye Research

SN - 1350-9462

M1 - 100843

ER -