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dc.contributor.authorBanning, Antje
dc.contributor.authorGülec, Christina
dc.contributor.authorRouvinen, Juha
dc.contributor.authorGray, Steven J.
dc.contributor.authorTikkanen, Ritva
dc.date.accessioned2022-11-18T09:51:45Z
dc.date.available2017-05-26T09:52:56Z
dc.date.available2022-11-18T09:51:45Z
dc.date.issued2016
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:hebis:26-opus-128529
dc.identifier.urihttps://jlupub.ub.uni-giessen.de//handle/jlupub/9274
dc.identifier.urihttp://dx.doi.org/10.22029/jlupub-8662
dc.description.abstractAspartylglucosaminuria (AGU) is a lysosomal storage disorder that is caused by genetic deficiency of the enzyme aspartylglucosaminidase (AGA) which is involved in glycoprotein degradation. AGU is a progressive disorder that results in severe mental retardation in early adulthood. No curative therapy is currently available for AGU. We have here characterized the consequences of a novel AGU mutation that results in Thr122Lys exchange in AGA, and compared this mutant form to one carrying the worldwide most common AGU mutation, AGU-Fin. We show that T122K mutated AGA is expressed in normal amounts and localized in lysosomes, but exhibits low AGA activity due to impaired processing of the precursor molecule into subunits. Coexpression of T122K with wildtype AGA results in processing of the precursor into subunits, implicating that the mutation causes a local misfolding that prevents the precursor from becoming processed. Similar data were obtained for the AGU-Fin mutant polypeptide. We have here also identified small chemical compounds that function as chemical or pharmacological chaperones for the mutant AGA. Treatment of patient fibroblasts with these compounds results in increased AGA activity and processing, implicating that these substances may be suitable for chaperone mediated therapy for AGU.en
dc.language.isoende_DE
dc.rightsNamensnennung 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddcddc:610de_DE
dc.titleIdentification of Small Molecule Compounds for Pharmacological Chaperone Therapy of Aspartylglucosaminuriaen
dc.typearticlede_DE
local.affiliationFB 11 - Medizinde_DE
local.opus.id12852
local.opus.instituteInstitute of Biochemistryde_DE
local.opus.fachgebietMedizinde_DE
local.source.urihttps://doi.org/10.1038/srep37583
local.source.freetextScientific Reports 6:37583de_DE


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