Differentially expressed proteins underlying childhood cortical dysplasia with epilepsy identified by iTRAQ proteomic
Lu Qin1, Xi Liu1, Shiyong Liu2
1Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Insights
This study identified key proteins in childhood cortical dysplasia, a cause of epilepsy. Researchers found specific proteins increased and others decreased, offering new research targets for this condition.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Cortical dysplasia is a significant cause of childhood epilepsy, affecting at least 14% of cases.
- The molecular mechanisms and pathogenesis of cortical dysplasia remain poorly understood.
- Limited knowledge exists regarding the specific protein alterations in childhood cortical dysplasia.
Purpose of the Study:
- To identify key molecules involved in the pathogenesis of cortical dysplasia.
- To screen and validate differentially expressed proteins in brain tissues of children with cortical dysplasia and epilepsy.
- To provide novel insights into the molecular underpinnings of childhood cortical dysplasia.
Main Methods:
- Utilized isobaric tags for relative and absolute quantitation-based tandem mass spectrometry (iTRAQ-MS/MS) for protein screening.
- Compared protein expression profiles between childhood cortical dysplasia patients with epilepsy and control subjects.
- Validated differentially expressed proteins using real-time polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry.
Main Results:
- Identified 153 differentially expressed proteins out of 3340 screened proteins between patients and controls.
- Found increased expression of FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, and FABP3 in childhood cortical dysplasia.
- Observed decreased expression of PRDX6 and PSAP in childhood cortical dysplasia patients.
Conclusions:
- This is the first report detailing differentially expressed proteins in childhood cortical dysplasia.
- The identified proteins (FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, FABP3, PRDX6, PSAP) are implicated in various cellular processes.
- These findings may offer new research directions and therapeutic targets for understanding and treating childhood cortical dysplasia.
Abstract:
Cortical dysplasia accounts for at least 14% of epilepsy cases, and is mostly seen in children. However, the understanding of molecular mechanisms and pathogenesis underlying cortical dysplasia is limited. The aim of this cross-sectional study is to identify potential key molecules in the mechanisms of cortical dysplasia by screening the proteins expressed in brain tissues of childhood cortical dysplasia patients with epilepsy using isobaric tags for relative and absolute quantitation-based tandem mass spectrometry compared to controls, and several differentially expressed proteins that are not reported to be associated with cortical dysplasia previously were selected for validation using real-time polymerase chain reaction, immunoblotting and immunohistochemistry. 153 out of 3340 proteins were identified differentially expressed between childhood cortical dysplasia patients and controls. And FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, and FABP3 were selected for validation and identified to be increased in childhood cortical dysplasia patients, while PRDX6 and PSAP were identified decreased. This is the first report on differentially expressed proteins in childhood cortical dysplasia. We identified differential expression of FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, FABP3, PRDX6 and PSAP in childhood cortical dysplasia patients, these proteins are involved in various processes and have various function. These results may provide new directions or targets for the research of childhood cortical dysplasia, and may be helpful in revealing molecular mechanisms and pathogenesis and/or pathophysiology of childhood cortical dysplasia if further investigated.
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