Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers
Premutation carriers have a 55-200 CGG expansion in the fragile X mental retardation 1 (FMR1) gene. Currently, 1.5 million individuals are affected in the United States, and carriers are at risk of developing the late-onset neurodegenerative disorder Fragile X-associated tremor ataxia syndrome (FXTA...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00071/full |
| _version_ | 1818671972836442112 |
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| author | Cecilia Giulivi Cecilia Giulivi Eleonora Napoli Flora Tassone Flora Tassone Julian Halmai Randi Hagerman Randi Hagerman |
| author_facet | Cecilia Giulivi Cecilia Giulivi Eleonora Napoli Flora Tassone Flora Tassone Julian Halmai Randi Hagerman Randi Hagerman |
| author_sort | Cecilia Giulivi |
| collection | DOAJ |
| description | Premutation carriers have a 55-200 CGG expansion in the fragile X mental retardation 1 (FMR1) gene. Currently, 1.5 million individuals are affected in the United States, and carriers are at risk of developing the late-onset neurodegenerative disorder Fragile X-associated tremor ataxia syndrome (FXTAS). Limited efforts have been made to develop new methods for improved early patient monitoring, treatment response and disease progression. To this end, plasma metabolomic phenotyping was obtained for 23 premutation carriers and 16 age- and sex-matched controls. Three biomarkers, phenylethylamine normalized by either aconitate or isocitrate and oleamide normalized by isocitrate, exhibited excellent model performance. The lower phenylethylamine and oleamide plasma levels in carriers may indicate, respectively, incipient nigrostriatal degeneration and higher incidence of substance abuse, anxiety and sleep disturbances. Higher levels of citrate, isocitrate, aconitate and lactate may reflect deficits in both bioenergetics and neurotransmitter metabolism (Glu, GABA). This study lays important groundwork by defining the potential utility of plasma metabolic profiling to monitor brain pathophysiology in carriers before and during the progression of FXTAS, treatment efficacy and evaluation of side effects. |
| first_indexed | 2024-12-17T07:32:30Z |
| format | Article |
| id | doaj.art-4991d42e749547f3b428efbc1d8e02b4 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-17T07:32:30Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-4991d42e749547f3b428efbc1d8e02b42022-12-21T21:58:26ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992016-08-01910.3389/fnmol.2016.00071216618Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriersCecilia Giulivi0Cecilia Giulivi1Eleonora Napoli2Flora Tassone3Flora Tassone4Julian Halmai5Randi Hagerman6Randi Hagerman7University of CaliforniaUniversity of California DavisUniversity of CaliforniaUniversity of California DavisUniversity of California DavisUniversity of CaliforniaUniversity of California DavisUniversity of California DavisPremutation carriers have a 55-200 CGG expansion in the fragile X mental retardation 1 (FMR1) gene. Currently, 1.5 million individuals are affected in the United States, and carriers are at risk of developing the late-onset neurodegenerative disorder Fragile X-associated tremor ataxia syndrome (FXTAS). Limited efforts have been made to develop new methods for improved early patient monitoring, treatment response and disease progression. To this end, plasma metabolomic phenotyping was obtained for 23 premutation carriers and 16 age- and sex-matched controls. Three biomarkers, phenylethylamine normalized by either aconitate or isocitrate and oleamide normalized by isocitrate, exhibited excellent model performance. The lower phenylethylamine and oleamide plasma levels in carriers may indicate, respectively, incipient nigrostriatal degeneration and higher incidence of substance abuse, anxiety and sleep disturbances. Higher levels of citrate, isocitrate, aconitate and lactate may reflect deficits in both bioenergetics and neurotransmitter metabolism (Glu, GABA). This study lays important groundwork by defining the potential utility of plasma metabolic profiling to monitor brain pathophysiology in carriers before and during the progression of FXTAS, treatment efficacy and evaluation of side effects.http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00071/fullFragile X SyndromeMetabolomicsneurodegenerationMitochondrial dysfunctionTrinucleotide repeat diseases |
| spellingShingle | Cecilia Giulivi Cecilia Giulivi Eleonora Napoli Flora Tassone Flora Tassone Julian Halmai Randi Hagerman Randi Hagerman Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers Frontiers in Molecular Neuroscience Fragile X Syndrome Metabolomics neurodegeneration Mitochondrial dysfunction Trinucleotide repeat diseases |
| title | Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers |
| title_full | Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers |
| title_fullStr | Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers |
| title_full_unstemmed | Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers |
| title_short | Plasma biomarkers for monitoring brain pathophysiology in FMR1 premutation carriers |
| title_sort | plasma biomarkers for monitoring brain pathophysiology in fmr1 premutation carriers |
| topic | Fragile X Syndrome Metabolomics neurodegeneration Mitochondrial dysfunction Trinucleotide repeat diseases |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00071/full |
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