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Updated: Aug 8, 2025

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
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Genetically Determined Levels of mTOR-Dependent Circulating Proteins and Risk of Multiple Sclerosis

Yao-Chen Zhang1,2,3, Ke-Yi Fan2,3, Qi Wang3,4,5

  • 1Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.

Neurology and Therapy
|March 4, 2023
PubMed
Abstract

Insights

Circulating levels of PKC-α may protect against multiple sclerosis (MS), while RP-S6K may increase MS risk. These findings suggest potential therapeutic targets for MS prevention and risk screening.

Area of Science:

  • Genetics
  • Immunology
  • Biochemistry

Background:

  • Observational studies suggest a link between mammalian target of rapamycin (mTOR)-dependent proteins and multiple sclerosis (MS) risk.
  • A causal relationship between these proteins and MS remains unclear.
  • Mendelian randomization (MR) is a robust method to investigate causal associations and mitigate bias.

Purpose of the Study:

  • To investigate the causal association between seven mTOR-dependent proteins and the risk of developing MS.
  • To determine if specific mTOR-dependent proteins act as risk or protective factors for MS.

Main Methods:

  • Utilized genome-wide association study (GWAS) summary statistics from large MS and healthy individual cohorts.
  • Employed multiple MR analysis methods (inverse variance weighted, weighted median, MR-Egger) to assess causality.
  • Conducted sensitivity analyses to ensure the robustness and reliability of the findings.

Main Results:

  • Elevated circulating levels of protein kinase C-alpha (PKC-α) were associated with a reduced risk of MS (OR 0.90, P=0.017).
  • Increased circulating levels of ribosomal protein S6 kinase (RP-S6K) were associated with an increased risk of MS (OR 1.12, P=0.045).
  • No significant causal associations were found for other studied mTOR-dependent proteins (AKT, eIF4E-BP, eIF4A, eIF4E, eIF4G).

Conclusions:

  • The mTOR signaling pathway plays a bidirectional role in the development of MS.
  • PKC-α acts as a protective factor, while RP-S6K acts as a risk factor for MS.
  • PKC-α and RP-S6K represent potential therapeutic targets for MS risk stratification and targeted prevention strategies.
Keywords:
Mendelian randomization analysisMolecular epidemiologyMultiple sclerosismTOR-associated protein

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