Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13.

Autor: Cariulo C; Department of Neuroscience, IRBM S.p.A, Via Pontina Km 30.600, 00071, Pomezia, Rome, Italy., Verani M; Department of Neuroscience, IRBM S.p.A, Via Pontina Km 30.600, 00071, Pomezia, Rome, Italy., Martufi P; Department of Neuroscience, IRBM S.p.A, Via Pontina Km 30.600, 00071, Pomezia, Rome, Italy., Ingenito R; Peptide Chemistry Unit, IRBM S.p.A., Via Pontina Km 30 600, 00071, Pomezia, Rome, Italy., Finotto M; Peptide Chemistry Unit, IRBM S.p.A., Via Pontina Km 30 600, 00071, Pomezia, Rome, Italy., Deguire SM; Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Station 19, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland., Lavery DJ; CHDI Management/CHDI Foundation, Los Angeles, CA, 90045, USA., Toledo-Sherman L; CHDI Management/CHDI Foundation, Los Angeles, CA, 90045, USA., Lee R; CHDI Management/CHDI Foundation, Princeton, NJ 08540, USA. Electronic address: ramee.lee@chdifoundation.org., Doherty EM; CHDI Management/CHDI Foundation, Los Angeles, CA, 90045, USA., Vogt TF; CHDI Management/CHDI Foundation, Princeton, NJ 08540, USA., Dominguez C; CHDI Management/CHDI Foundation, Los Angeles, CA, 90045, USA., Lashuel HA; Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Station 19, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland., Petricca L; Department of Neuroscience, IRBM S.p.A, Via Pontina Km 30.600, 00071, Pomezia, Rome, Italy., Caricasole A; Department of Neuroscience, IRBM S.p.A, Via Pontina Km 30.600, 00071, Pomezia, Rome, Italy.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Jan 15; Vol. 521 (3), pp. 549-554. Date of Electronic Publication: 2019 Oct 31.
DOI: 10.1016/j.bbrc.2019.09.097
Abstrakt: 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.
(Copyright © 2019. Published by Elsevier Inc.)
Databáze: MEDLINE
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