Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13.

Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13.

Publication date: Oct 30, 2019

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by an expansion of a CAG triplet repeat (encoding for a polyglutamine tract) within the first exon of the huntingtin gene. Expression of the mutant huntingtin (mHTT) protein can result in the production of N-terminal fragments with a robust propensity to form oligomers and aggregates, which may be causally associated with HD pathology. Several lines of evidence indicate that N17 phosphorylation or pseudophosphorylation at any of the residues T3, S13 or S16, alone or in combination, modulates mHTT aggregation, subcellular localization and toxicity. Consequently, increasing N17 phosphorylation has been proposed as a potential therapeutic approach. However, developing genetic/pharmacological tools to quantify these phosphorylation events is necessary in order to subsequently develop tool modulators, which is difficult given the transient and incompletely penetrant nature of such post-translational modifications. Here we describe the first ultrasensitive sandwich immunoassay that quantifies HTT phosphorylated at residue S13 and demonstrate its utility for specific analyte detection in preclinical models of HD.

Cariulo, C., Verani, M., Martufi, P., Ingenito, R., Finotto, M., Deguire, S.M., Lavery, D.J., Toledo-Sherman, L., Lee, R., Doherty, E.M., Vogt, T.F., Dominguez, C., Lashuel, H.A., Petricca, L., and Caricasole, A. Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13. 06746. 2019 Biochem Biophys Res Commun.

Concepts Keywords
Analyte Branches of biology
Exon Cell biology
Gene Phosphorus
Genetic Cell signaling
Huntingtin Huntingtin
Huntington Huntington’s disease
Immunoassay Posttranslational modification
Mutant HTT
N Terminal Phosphorylation
N17 Analyte
Neurodegenerative Disorder Post-translational modification
Oligomers Gene Expression
Pathology
Penetrant
Pharmacological
Phosphorylated
Phosphorylation
Progressive
Sandwich
Subcellular Localization
Toxicity
Triplet

Semantics

Type Source Name
gene UNIPROT HTT
disease MESH neurodegenerative disorder
gene UNIPROT NUP214
gene UNIPROT DESI1
gene UNIPROT SLC35G1

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