Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease)
| العنوان: | Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease) |
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| المؤلفون: | Jonathan P. Dyke, Barry E. Kosofsky, Dolan Sondhi, Douglas Ballon, Stephen M. Kaminsky, Miriam Sindelar, Ronald G. Crystal, Steven S. Gross, Ruba S. Deeb |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Metabolite, lcsh:Medicine, Disease, Acetates, Aminopeptidases, Severity of Illness Index, chemistry.chemical_compound, Cerebrospinal fluid, Child, lcsh:Science, Neurons, Multidisciplinary, Tripeptidyl-Peptidase 1, Neurodegeneration, Brain, Middle Aged, 3. Good health, Mitochondria, Child, Preschool, Metabolome, Female, Adult, Batten disease, Adolescent, Article, Lipofuscin, 03 medical and health sciences, Young Adult, Metabolomics, Neuronal Ceroid-Lipofuscinoses, Severity of illness, medicine, Animals, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Aged, business.industry, lcsh:R, medicine.disease, Disease Models, Animal, 030104 developmental biology, chemistry, Immunology, lcsh:Q, Serine Proteases, business, Biomarkers |
| الوصف: | Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a rare lysosomal storage disorder caused by a monogenetic deficiency of tripeptidyl peptidase-1 (TPP1). Despite knowledge that lipofuscin is the hallmark disease product, the relevant TPP1 substrate and its role in neuronal physiology/pathology is unknown. We hypothesized that untargeted metabolite profiling of cerebrospinal fluid (CSF) could be used as an effective tool to identify disease-associated metabolic disruptions in CLN2 disease, offering the potential to identify biomarkers that inform on disease severity and progression. Accordingly, a mass spectrometry-based untargeted metabolite profiling approach was employed to differentiate CSF from normal vs. CLN2 deficient individuals. Of 1,433 metabolite features surveyed, 29 linearly correlated with currently employed disease severity scores. With tandem mass spectrometry 8 distinct metabolite identities were structurally confirmed based on retention time and fragmentation pattern matches, vs. standards. These putative CLN2 biomarkers include 7 acetylated species – all attenuated in CLN2 compared to controls. Because acetate is the major bioenergetic fuel for support of mitochondrial respiration, deficient acetylated species in CSF suggests a brain energy defect that may drive neurodegeneration. Targeted analysis of these metabolites in CSF of CLN2 patients offers a powerful new approach for monitoring CLN2 disease progression and response to therapy. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7aa2f254033554dfd856fcfa9bfb12fcTest http://link.springer.com/article/10.1038/s41598-018-33449-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7aa2f254033554dfd856fcfa9bfb12fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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