DNA damage signatures in peripheral blood cells (PBMC) as biomarkers in prodromal Huntington's disease
| Autor: | Antonio Porcellini, Elena Salvatore, Giuseppe De Michele, Simone Migliore, Silvio Peluso, Antonella Romano, Angelo Del Mondo, Candida Zuchegna, Ferdinando Squitieri, Rosella Mechelli, Mariarosaria De Rosa, Enrico V. Avvedimento, Imma Castaldo, Cristiana Borrelli, Silvia Romano, Giovanni Ristori, Luigi Angelo Vescovi |
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| Přispěvatelé: | Castaldo, Imma, De Rosa, Mariarosaria, Romano, Antonella, Zuchegna, Candida, Squitieri, Ferdinando, Mechelli, Rosella, Peluso, Silvio, Borrelli, Cristiana, Del Mondo, Angelo, Salvatore, Elena, Vescovi, Luigi Angelo, Migliore, Simone, De Michele, Giuseppe, Ristori, Giovanni, Romano, Silvia, Avvedimento, Enrico, Porcellini, Antonio |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty huntington's disease Neurology DNA damage Prodromal Symptoms Peripheral blood mononuclear cell Histones Young Adult 03 medical and health sciences 0302 clinical medicine Humans Medicine age-of-onset Phosphorylation Gene Aged biology business.industry Case-control study Middle Aged Telomere Flow Cytometry Huntington Disease 030104 developmental biology Histone Case-Control Studies Immunology Leukocytes Mononuclear biology.protein Biomarker (medicine) Female dna damage protein Neurology (clinical) business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Annals of Neurology. |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.25393 |
| Popis: | Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1-6 ANN NEUROL 2019;85:296-301. |
| Databáze: | OpenAIRE |
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