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Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy
J W Yang1, T Czech, M Felizardo
1Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Abstract:
Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is characterised by cytoarchitectural abnormalities including neuronal cell loss and reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein expression by proteomics techniques may help to understand pathomechanism that is still elusive. We searched for differential expression of hippocampal proteins by an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry unambiguously identifying 77 proteins analysed in eight control and eight MTLE hippocampi. Proteins were quantified and we observed 18 proteins that were altered in MTLE. Cytoskeleton proteins tubulin alpha-1 chain, beta-tubulin, profilin II, neuronal tropomodulin were significantly reduced and one actin spot was missing, whereas ezrin and vinculin were significantly increased in MTLE. Proteins of several classes as e.g. antioxidant proteins (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-alpha, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, alpha-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in MTLE. Taken together, the findings may represent or lead to cytoskeletal impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD-dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms and altered synaptosomal protein expression possibly reflects synaptic impairment in MTLE.
Insights
Mesial temporal lobe epilepsy (MTLE) involves hippocampal changes. Proteomics revealed altered cytoskeleton proteins, suggesting impairment and potential synaptic damage in MTLE.
Area of Science:
- Neuroscience
- Molecular Biology
- Epilepsy Research
Background:
- Mesial temporal lobe epilepsy (MTLE) is the most common epilepsy type.
- It features hippocampal cytoarchitectural abnormalities like neuronal loss and gliosis.
- The underlying pathomechanism of MTLE remains incompletely understood.
Purpose of the Study:
- To investigate differential hippocampal protein expression in MTLE using proteomics.
- To identify specific proteins, particularly cytoskeleton proteins, altered in MTLE.
- To gain insights into the pathogenetic mechanisms of MTLE.
Main Methods:
- Proteomics analysis using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry.
- Analysis of hippocampal tissue from eight control and eight MTLE subjects.
- Quantification of protein expression levels to identify differentially expressed proteins.
Main Results:
- Seventy-seven hippocampal proteins were identified and analyzed.
- Eighteen proteins showed altered expression in MTLE hippocampi.
- Key findings include reduced levels of tubulin, profilin II, and neuronal tropomodulin, and increased ezrin and vinculin. Several other protein classes were also altered.
Conclusions:
- The study identified significant alterations in hippocampal cytoskeleton proteins in MTLE.
- Aberrant expression of antioxidant proteins, chaperones, MAP kinase kinase 1, and NAD-dependent deacetylase sirtuin-2 may contribute to MTLE pathogenesis.
- Altered synaptosomal protein expression suggests potential synaptic impairment in MTLE.
