Fukutin-Related Protein: From Pathology to Treatments

Fukutin-related protein (FKRP) is a glycosyltransferase involved in the functional glycosylation of α-dystroglycan (DG), a key component in the link between the cytoskeleton and the extracellular matrix (ECM). Mutations in FKRP lead to dystroglycanopathies with broad severity, including limb-girdle...

Full description

Saved in:
Bibliographic Details
Published in:Trends in cell biology 2021-03, Vol.31 (3), p.197-210
Main Authors: Ortiz-Cordero, Carolina, Azzag, Karim, Perlingeiro, Rita C.R.
Format: Article
Language:English
Subjects:
Cell therapy
congenital muscular dystrophy
Cytoskeleton
Dystroglycan
dystroglycanopathy
Dystroglycans - genetics
Dystroglycans - metabolism
Dystrophy
Extracellular matrix
FCMD protein
Gene transfer
Glycosylation
Glycosyltransferase
Glycosyltransferases - metabolism
Humans
limb-girdle
Muscular Dystrophies - genetics
Muscular Dystrophies - therapy
Muscular dystrophy
Mutation
Pentosyltransferases - genetics
Pentosyltransferases - metabolism
Proteins
α-dystroglycan
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fukutin-related protein (FKRP) is a glycosyltransferase involved in the functional glycosylation of α-dystroglycan (DG), a key component in the link between the cytoskeleton and the extracellular matrix (ECM). Mutations in FKRP lead to dystroglycanopathies with broad severity, including limb-girdle and congenital muscular dystrophy. Studies over the past 5 years have elucidated the function of FKRP, which has expanded the number of therapeutic opportunities for patients carrying FKRP mutations. These include small molecules, gene delivery, and cell therapy. Here we summarize recent findings on the function of FKRP and describe available models for studying diseases and testing therapeutics. Lastly, we highlight preclinical studies that hold potential for the treatment of FKRP-associated dystroglycanopathies. FKRP is a ribitol-5-phosphate transferase involved in α-DG glycosylation. Mutations in FKRP have been associated with a broad spectrum of dystroglycanopathies.Several FKRP mutant models have been generated to better understand disease pathogenesis of FKRP-associated dystroglycanopathies as well as to develop therapeutics.Several strategies, including the use of small molecules, gene therapy, and cell therapy, have shown improvement of disease phenotype as evidenced by rescue of α-DG functional glycosylation.
ISSN:0962-8924
1879-3088
DOI:10.1016/j.tcb.2020.11.003