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Peptidome analysis of cerebrospinal fluid by LC-MALDI MS.

Hölttä M, Zetterberg H, Mirgorodskaya E, Mattsson N, Blennow K, Gobom J - PLoS ONE (2012)

Bottom Line: Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features.Out of these, 730 peptides were identified by MS/MS.The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders.

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Related in: MedlinePlus

Peptides identified from the Granin family.(a) Chromogranin- A (CMGA), (b) Secretogranin 1 (SCG1), (c) Secretogranin 2 (SCG2), (d) Neurosecretory protein VGF (VGF).
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pone-0042555-g006: Peptides identified from the Granin family.(a) Chromogranin- A (CMGA), (b) Secretogranin 1 (SCG1), (c) Secretogranin 2 (SCG2), (d) Neurosecretory protein VGF (VGF).

Mentions: Peptides from the granin family have been discussed as CSF biomarkers for various diseases such as AD, multiple sclerosis, schizophrenia, and depression [44]. The granins (Chromogranin-A (CMGA), Secretogranin-1 (SCG1), Secretogranin-2 (SCG2), Secretogranin-3, 7B2, NESP22, proSAAS, and VGF) are involved in regulated delivery of several key factors in CNS such as neurotransmitters, hormones and growth factors. Peptides from Neurosecretory protein VGF have been associated with different brain disorders, such as VGF26–62[45] with decreased levels in frontotemporal dementia; VGF378–397[46], [47], with decreased levels in AD; VGF23–62[48], with increased levels in schizophrenia and in depression; and SCG2529–566[48], with decreased levels in depression. In our study three of the peptides (VGF26–62, VGF23–62, and SCG2529–566) were found both as intact peptides and in truncated forms, while the third VGF peptide was only found as peptides exceeding the sequence length with 1–6 amino acids. In the case of SCG2 and CMGA, an alteration in three peptides is described as potential marker for multiple sclerosis, decreased SCG1441–493[49] and SCG1306–365[49] and increased CMGA194–213[50], [51]. SCG1441–493 has also been found decreased in frontotemporal dementia [45]. Although we did not identify any of SCG1441–493, SCG1306–365, or CMGA194–213 as intact peptides, we identified several forms spanning parts of these sites (Figure 6).


Peptidome analysis of cerebrospinal fluid by LC-MALDI MS.

Hölttä M, Zetterberg H, Mirgorodskaya E, Mattsson N, Blennow K, Gobom J - PLoS ONE (2012)

Peptides identified from the Granin family.(a) Chromogranin- A (CMGA), (b) Secretogranin 1 (SCG1), (c) Secretogranin 2 (SCG2), (d) Neurosecretory protein VGF (VGF).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412831&req=5

pone-0042555-g006: Peptides identified from the Granin family.(a) Chromogranin- A (CMGA), (b) Secretogranin 1 (SCG1), (c) Secretogranin 2 (SCG2), (d) Neurosecretory protein VGF (VGF).
Mentions: Peptides from the granin family have been discussed as CSF biomarkers for various diseases such as AD, multiple sclerosis, schizophrenia, and depression [44]. The granins (Chromogranin-A (CMGA), Secretogranin-1 (SCG1), Secretogranin-2 (SCG2), Secretogranin-3, 7B2, NESP22, proSAAS, and VGF) are involved in regulated delivery of several key factors in CNS such as neurotransmitters, hormones and growth factors. Peptides from Neurosecretory protein VGF have been associated with different brain disorders, such as VGF26–62[45] with decreased levels in frontotemporal dementia; VGF378–397[46], [47], with decreased levels in AD; VGF23–62[48], with increased levels in schizophrenia and in depression; and SCG2529–566[48], with decreased levels in depression. In our study three of the peptides (VGF26–62, VGF23–62, and SCG2529–566) were found both as intact peptides and in truncated forms, while the third VGF peptide was only found as peptides exceeding the sequence length with 1–6 amino acids. In the case of SCG2 and CMGA, an alteration in three peptides is described as potential marker for multiple sclerosis, decreased SCG1441–493[49] and SCG1306–365[49] and increased CMGA194–213[50], [51]. SCG1441–493 has also been found decreased in frontotemporal dementia [45]. Although we did not identify any of SCG1441–493, SCG1306–365, or CMGA194–213 as intact peptides, we identified several forms spanning parts of these sites (Figure 6).

Bottom Line: Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features.Out of these, 730 peptides were identified by MS/MS.The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders.

Show MeSH
Related in: MedlinePlus