4.7 Article

Association between Decreased ITGA7 Levels and Increased Muscle α-Synuclein in an MPTP-Induced Mouse Model of Parkinson's Disease

Journal

Publisher

MDPI
DOI: 10.3390/ijms23105646

Keywords

Parkinson's disease; ITGA7; alpha-synuclein; MPTP; muscle

Funding

  1. National Research Foundation of Korea (NRF) - Korean Government's Ministry of Science, ICT and Future Planning (MSIP) [2020R1I1A3A04036500]
  2. Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health andWelfare, Korea [HF20C0019]
  3. National Research Foundation of Korea [2020R1I1A3A04036500] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study investigated the potential relationship between ITGA7 and alpha-syn in the muscle of MPTP-induced mice and C2C12 cells. The results suggest that decreased ITGA7 expression in muscle could increase alpha-syn expression, which may contribute to the pathology of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN), reducing dopaminergic levels in the striatum and affecting motor control. Herein, we investigated the potential relationship between integrin alpha 7 (ITGA7) and alpha-synuclein (alpha-syn) in the muscle of methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced mice and C2C12 cells. To characterize the pathology of PD, we examined the expression of tyrosine hydroxylase (TH) in the SN of the midbrain. Compared with the control group, MPTP-treated mice showed a significant decrease in TH expression in the SN, accompanied by a significant decrease in muscle ITGA7 expression. Compared with the control group, alpha-syn expression was increased in the MPTP group. Furthermore, the pattern of alpha-syn expression in the MPTP group was similar to the ITGA7 expression pattern in the control group (linear forms). To determine the relationship between ITGA7 and PD, we examined the expression of ITGA7 and alpha-syn after ITGA7 knockdown using siRNA in C2C12 cells. ITGA7 expression significantly decreased while alpha-syn expression significantly increased in siRNA-treated C2C12 cells. These results suggest that decreased ITGA7 muscle expression could increase alpha-syn expression. Moreover, alpha-syn accumulation, induced by decreased muscle ITGA7, might contribute to PD pathology.

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