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Srpk3 Decrease Associated with Alpha-Synuclein Increase in Muscles of MPTP-Induced Parkinson's Disease Mice.

Min Hyung Seo1, Sujung Yeo1,2

  • 1Department of Meridian and Acupoint, College of Korean Medicine, Sang Ji University, Wonju 26339, Korea.

International Journal of Molecular Sciences
|September 10, 2021
PubMed
Summary

Parkinson's disease (PD) involves muscle pathology. Reduced serine/arginine-rich protein specific kinase 3 (srpk3) expression in muscles correlates with increased alpha-synuclein (α-syn) in PD models.

Keywords:
MPTPParkinson’s diseasealpha-synucleinmusclesrpk3

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Muscle Physiology

Background:

  • Parkinson's disease (PD) is marked by dopaminergic cell loss and α-synuclein (α-syn) aggregates (Lewy bodies/neurites).
  • Lewy pathology extends beyond the brain to peripheral tissues, including muscles, suggesting a systemic role in PD.
  • The specific molecular mechanisms linking muscle pathology and PD progression remain incompletely understood.

Purpose of the Study:

  • To investigate the relationship between serine/arginine-rich protein specific kinase 3 (srpk3) and α-syn expression in muscle tissue within Parkinson's disease.
  • To elucidate the potential role of srpk3 in the pathogenesis of muscle-related Lewy body pathology in PD.

Main Methods:

  • Utilized a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, specifically examining the quadriceps femoris muscle.
  • Employed the C2C12 myoblast cell line treated with 1-methyl-4-phenylpyridinium (MPP+) and srpk3 short interfering RNA (siRNA) for in vitro studies.
  • Quantified the expression levels of srpk3 and α-syn (including phosphorylated forms) using molecular biology techniques.

Main Results:

  • MPTP-induced PD mice exhibited significantly decreased srpk3 expression and increased α-syn expression in thigh muscles compared to controls.
  • MPP+ treatment of C2C12 cells dose-dependently reduced srpk3 expression while elevating α-syn expression.
  • Silencing srpk3 in C2C12 cells using siRNA led to increased expression of both α-syn and phosphorylated α-syn.

Conclusions:

  • MPTP intoxication alters srpk3 expression in muscles, potentially influencing α-syn expression and contributing to PD pathology.
  • These findings suggest srpk3 plays a regulatory role in α-syn aggregation within muscle tissue relevant to Parkinson's disease.
  • Further research into srpk3's mechanism in PD pathogenesis is warranted, particularly concerning its impact on peripheral tissues.