Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases
Abstract Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with c...
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Springer
2024-12-01
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| Series: | Amino Acids |
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| Online Access: | https://doi.org/10.1007/s00726-024-03434-1 |
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| author | Katharina Küper Gernot Poschet Julia Rossmann Sven F. Garbade Alexander Spiegelhalter Dan Wen Georg F. Hoffmann Claus P. Schmitt Thomas Opladen Verena Peters |
| author_facet | Katharina Küper Gernot Poschet Julia Rossmann Sven F. Garbade Alexander Spiegelhalter Dan Wen Georg F. Hoffmann Claus P. Schmitt Thomas Opladen Verena Peters |
| author_sort | Katharina Küper |
| collection | DOAJ |
| description | Abstract Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy. A panel of 33 DPs was quantified using UPLC-MS/MS. Out of 33 DPs, 18 were detectable in CSF and 20 in plasma, displaying high inter-individual variance. Gly-Asp, Gly-Pro, and Ala-Glu were consistently found in all CSF samples, while only Gly-Asp was universally detectable in plasma. Anserine and carnosine were prominent in CSF and plasma, respectively, with no other histidine-containing DPs observed. Generally, DP concentrations were higher in plasma than in CSF; however, anserine and Gly-Pro had similar concentrations in both fluids. Significant correlations were observed between specific DPs and their corresponding AAs in CSF (Gly-Glu, Gly-Pro and Ser-Gln) and plasma (Glu-Glu and Glu-Ser). Notably, patients with epilepsy had elevated medium anserine concentrations in CSF. This study is the first to demonstrate the presence of numerous DPs in CSF and plasma. Further research is needed to determine if DP patterns can support the diagnosis of neurological diseases and whether DP administration can modulate amino acid availability in the brain, potentially offering new therapeutic options, such as for defects in the amino acid transporter. |
| format | Article |
| id | doaj-art-e34278e04c2143718b47eee2a341b637 |
| institution | OA Journals |
| issn | 1438-2199 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Amino Acids |
| spelling | doaj-art-e34278e04c2143718b47eee2a341b6372025-08-20T02:37:54ZengSpringerAmino Acids1438-21992024-12-015711910.1007/s00726-024-03434-1Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseasesKatharina Küper0Gernot Poschet1Julia Rossmann2Sven F. Garbade3Alexander Spiegelhalter4Dan Wen5Georg F. Hoffmann6Claus P. Schmitt7Thomas Opladen8Verena Peters9Division of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityCentre for Organismal Studies (COS), Metabolomics Core Technology Platform, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityCentre for Organismal Studies (COS), Metabolomics Core Technology Platform, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg UniversityAbstract Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy. A panel of 33 DPs was quantified using UPLC-MS/MS. Out of 33 DPs, 18 were detectable in CSF and 20 in plasma, displaying high inter-individual variance. Gly-Asp, Gly-Pro, and Ala-Glu were consistently found in all CSF samples, while only Gly-Asp was universally detectable in plasma. Anserine and carnosine were prominent in CSF and plasma, respectively, with no other histidine-containing DPs observed. Generally, DP concentrations were higher in plasma than in CSF; however, anserine and Gly-Pro had similar concentrations in both fluids. Significant correlations were observed between specific DPs and their corresponding AAs in CSF (Gly-Glu, Gly-Pro and Ser-Gln) and plasma (Glu-Glu and Glu-Ser). Notably, patients with epilepsy had elevated medium anserine concentrations in CSF. This study is the first to demonstrate the presence of numerous DPs in CSF and plasma. Further research is needed to determine if DP patterns can support the diagnosis of neurological diseases and whether DP administration can modulate amino acid availability in the brain, potentially offering new therapeutic options, such as for defects in the amino acid transporter.https://doi.org/10.1007/s00726-024-03434-1DipeptideCSFEpilepsy |
| spellingShingle | Katharina Küper Gernot Poschet Julia Rossmann Sven F. Garbade Alexander Spiegelhalter Dan Wen Georg F. Hoffmann Claus P. Schmitt Thomas Opladen Verena Peters Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases Amino Acids Dipeptide CSF Epilepsy |
| title | Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases |
| title_full | Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases |
| title_fullStr | Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases |
| title_full_unstemmed | Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases |
| title_short | Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases |
| title_sort | dipeptides in csf and plasma diagnostic and therapeutic potential in neurological diseases |
| topic | Dipeptide CSF Epilepsy |
| url | https://doi.org/10.1007/s00726-024-03434-1 |
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