Abstract

Parkinson’s disease (PD) is characterized by a loss of dopaminergic cells in the substantia nigra, and its histopathological features include the presence of fibrillar aggregates of α-synuclein (α-syn), which are called Lewy bodies and Lewy neurites. Lewy pathology has been identified not only in the brain but also in various tissues, including muscles. This study aimed to investigate the link between serine/arginine-rich protein specific kinase 3 (srpk3) and α-syn in muscles in PD. We conducted experiments on the quadriceps femoris of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and the C2C12 cell line after treatment with 1-methyl-4-phenylpyridinium (MPP+) and srpk3 short interfering RNA (siRNA). Compared to the control group, the MPTP group showed significantly reduced expression of srpk3, but increased expression of α-syn. In MPP+-treated C2C12 cells, srpk3 expression gradually decreased and α-syn expression increased with the increasing MPP+ concentration. Moreover, experiments in C2C12 cells using srpk3 siRNA showed increased expressions of α-syn and phosphorylated α-syn. Our results showed that srpk3 expression could be altered by MPTP intoxication in muscles, and this change may be related to changes in α-syn expression. Furthermore, this study could contribute to advancement of research on the mechanism by which srpk3 plays a role in PD.

Highlights

  • Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic cell loss in the substantia nigra (SN)

  • TuhsecpleusrpionseaoPf tDhismouse model. sFtuudrythwerams toorein, vthesitsigsattuedtyhecoliunkldbceotwnetreinbusrtpekt3oaanddvαa-nscyinnginrmesuesacrlecshionnatPhDe mmeocuhseanism of srpk3 masodaenl. eFluermtheernmt orreel,attheids sttoudPyDco. uld contribute to advancing research on the mechanism of srpk3 as an element related to PD

  • Our results showed an increased expression of mef2 in the MPTP parkinsonism mouse and MPP+-treated C2C12 cells, whereas srpk2 expression was decreased in these models

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Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic cell loss in the substantia nigra (SN). The main symptoms of PD are motor dysfunction, including bradykinesia, tremor, muscle rigidity, postural instability, and walking impairments. Exercise improves motor function in patients with PD [12,13]. Consistent exercise and engaging in regular exercise are associated with significant positive effects on health-related quality of life and motor function changes [14]. The study of aerobic exercise showed generic health benefits for people with PD, including a reduced incidence of mortality and cardiovascular disease and improved bone health [16]. These studies suggest a link between muscle-related factors and PD

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