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Elevation of Proenkephalin 143-183 in Cerebrospinal Fluid in Moyamoya Disease
Kinya Yokoyama1, Mikio Maruwaka1, Kazuhiro Yoshikawa2
1Department of Neurosurgery, Nagoya University Graduate School of Medicine, Aichi, Japan.
Background:
In moyamoya disease (MMD), the causes of differences in clinical features between children and adults and of the dramatic temporal changes in moyamoya vessels are poorly understood. We previously discovered elevated levels of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid (CSF) in patients with MMD. This study examined the amino acid sequences of these peptides and quantified in specimens.
Methods:
The m/z 4588 and m/z 4473 peptides in CSF from patients with MMD were purified and concentrated by high-performance liquid chromatography and ultrafiltration. Liquid chromatography coupled with tandem mass spectrometry analysis was performed to identify the amino acid sequences of these peptides. We quantified these peptides in samples using sandwich enzyme-linked immunosorbent assay, and concentrations in CSF were compared between MMD (n = 40, 19 male; median age, 37 years) and non-MMD intracranial disease (n = 40, 19 male; median age, 39 years) as controls.
Results:
These peptides were identified as proenkephalin 143-183 (PENK 143-183). The concentration of PENK 143-183 was significantly greater in patients with MMD (median, 8,270 pmol/L) than control patients (median, 3,760 pmol/L; P < 0.001) and decreased in an age-dependent manner in MMD (r = -0.57; P < 0.001). The area under the receiver operating characteristic curve in children (age <18 years) was 0.885 (95% confidence interval 0.741-1). The correlation between proenkephalin concentration and temporal changes in moyamoya vessels was suggested.
Conclusions:
Proenkephalin 143-183 in CSF may offer a helpful diagnostic biomarker in pediatric MMD. The effect of enkephalin peptides through opioid growth factor receptor or delta opioid receptor might be associated with the pathophysiology of MMD.
Insights
Elevated proenkephalin 143-183 (PENK 143-183) in cerebrospinal fluid (CSF) may diagnose pediatric moyamoya disease (MMD). This biomarker shows potential for understanding MMD
Area of Science:
- Neuroscience
- Biochemistry
- Medical Diagnostics
Background:
- Moyamoya disease (MMD) pathophysiology, particularly age-related clinical differences and vascular changes, remains unclear.
- Previous research identified elevated m/z 4588 and m/z 4473 peptides in MMD patient cerebrospinal fluid (CSF).
Purpose of the Study:
- To identify the amino acid sequences of previously discovered peptides in MMD CSF.
- To quantify these peptides in MMD patients and compare them to controls.
- To investigate the potential of these peptides as diagnostic biomarkers for MMD, especially in children.
Main Methods:
- Peptides from MMD patient CSF were purified using high-performance liquid chromatography and ultrafiltration.
- Liquid chromatography-tandem mass spectrometry identified the peptide sequences.
- Sandwich enzyme-linked immunosorbent assays quantified peptide concentrations in CSF from MMD patients (n=40) and controls (n=40).
Main Results:
- The peptides were identified as proenkephalin 143-183 (PENK 143-183).
- PENK 143-183 concentrations were significantly higher in MMD patients (median 8,270 pmol/L) than controls (median 3,760 pmol/L; P < 0.001).
- PENK 143-183 levels decreased with age in MMD patients (r=-0.57; P < 0.001), with high diagnostic accuracy in children (AUC=0.885).
Conclusions:
- PENK 143-183 in CSF is a promising diagnostic biomarker for pediatric moyamoya disease.
- Enkephalin peptide interactions with opioid receptors may play a role in MMD pathophysiology.