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Phosphorylation of S6 Protein as a Potential Biomarker in Surgically Treated Refractory Epilepsy

Felipe I Chodraui1, Camila Araújo B Garcia1, Niele D Mendes1

  • 1Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, Brazil.

Developmental Neuroscience
|March 11, 2021
PubMed

Insights

Phosphorylated protein S6 (pS6) may be a reliable biomarker for epilepsy. Increased pS6 marking in tuberous sclerosis complex, focal cortical dysplasia IIB, and hemimegalencephaly correlates with more severe mTOR-dependent brain anomalies.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Tuberous sclerosis complex (TSC), focal cortical dysplasia IIB (FCD IIB), and hemimegalencephaly (HME) share mTOR pathway hyperactivation.
  • These conditions are linked to refractory epilepsy requiring surgical intervention with variable outcomes.
  • Phosphorylated protein S6 (pS6) is a downstream mTOR target, but its expression can be elevated without pathway alteration.

Purpose of the Study:

  • To investigate pS6 as a potential biomarker in epilepsy.
  • To quantify pS6 expression in TSC, FCD IIB, and HME patient brain specimens.
  • To correlate pS6 levels with clinical features of these mTOR-dependent brain anomalies.

Main Methods:

  • Immunohistochemical marking and quantification of pS6.
  • Analysis of 26 resected brain specimens from patients with TSC, FCD IIB, or HME.
  • Comparison with pS6 data from a control group of 25 patients.

Main Results:

  • pS6 expression was analyzed in patient cohorts.
  • Quantification revealed varying degrees of pS6 positivity.
  • A higher percentage of pS6 marking was associated with more severe mTOR-dependent brain anomalies.

Conclusions:

  • pS6 shows promise as a reliable biomarker in epilepsy.
  • Elevated pS6 levels may indicate increased severity in mTOR-related brain disorders.
  • Further research can explore pS6's role in guiding epilepsy treatment strategies.
Keywords:
BiomarkerEpilepsyProtein S6Surgery

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