Titolo | A Functional Human Glycogen Debranching Enzyme Encoded by a Synthetic Gene: Its Implications for Glycogen Storage Disease Type III Management |
---|---|
Tipo di pubblicazione | Articolo su Rivista peer-reviewed |
Anno di Pubblicazione | 2024 |
Autori | Triggiani, Doriana, Demurtas Olivia Costantina, Illiano Elena, Massa Silvia, Pasquo A., Dionisi-Vici Carlo, Marino Carmela, Giuliano Giovanni, and Franconi Rosella |
Rivista | Protein and Peptide Letters |
Volume | 31 |
Paginazione | 519 – 531 |
Type of Article | Article |
ISSN | 09298665 |
Parole chiave | Agl gene, animal tissue, article, cellular distribution, codon, complementary DNA, controlled study, enzyme activity, enzyme replacement, Escherichia coli, gene, Gene expression, gene replacement therapy, genetic transfection, glycogen debranching enzyme, glycogen storage disease type 3, HEK293 cell line, human, human cell, nonhuman, rat |
Abstract | Background: Glycogen Storage Disease type III (GSD III) is a metabolic disorder resulting from a deficiency of the Glycogen Debranching Enzyme (GDE), a large monomeric protein (approximately 170 kDa) with cytoplasmic localization and two distinct enzymatic activities: 4-α-glucantransferase and amylo-α-1,6-glucosidase. Mutations in the Agl gene, with consequent deficiency in GDE, lead to the accumulation of abnormal/toxic glycogen with shorter chains (phosphorylase limit dextrin, PLD) in skeletal and/or heart muscle and/or in the liver. Currently, there is no targeted therapy, and available treatments are symptomatic, relying on specific diets. Methods: Enzyme Replacement Therapy (ERT) might represent a potential therapeutic strategy for GSD III. Moreover, the single-gene nature of GSD III, the subcellular localization of GDE, and the type of affected tissues represent ideal conditions for exploring gene therapy approaches. Toward this direction, we designed a synthetic, codon-optimized cDNA encoding the human GDE. Results: This gene yielded high amounts of soluble, enzymatically active protein in Escherichia coli. Moreover, when transfected in Human Embryonic Kidney cells (HEK-293), it successfully encoded a functional GDE. Conclusion: These results suggest that our gene or protein might complement the missing function in GSD III patients, opening the door to further exploration of therapeutic approaches for this disease. © 2024 Bentham Science Publishers. |
Note | Cited by: 0 |
URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85203360528&doi=10.2174%2f0109298665307430240628063339&partnerID=40&md5=bf1333d01ff0dcef1f6237bf82261bb8 |
DOI | 10.2174/0109298665307430240628063339 |
Citation Key | Triggiani2024519 |
PubMed ID | 39021187 |