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

Abstract

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 α7 (ITGA7) and α-synuclein (α-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, α-syn expression was increased in the MPTP group. Furthermore, the pattern of α-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 α-syn after ITGA7 knockdown using siRNA in C2C12 cells. ITGA7 expression significantly decreased while α-syn expression significantly increased in siRNA-treated C2C12 cells. These results suggest that decreased ITGA7 muscle expression could increase α-syn expression. Moreover, α-syn accumulation, induced by decreased muscle ITGA7, might contribute to PD pathology.

Proteomic Analysis Reveals the Effects of Different Dietary Protein Levels on Growth and Development of Jersey-Yak

“…Among them, the integrin subunit alpha 7 (ITGA7) protein is mainly expressed in skeletal muscle and myocardium, and it may be involved in differentiation and migration during myogenesis. The defect of this gene is associated with congenital myopathy [39][40][41]. In addition, studies have found that ITGA7 plays an important role in the early stages of osteogenesis by upregulating the PI3K-AKT signaling pathway [39].…”

Impaired skeletal muscle health in Parkinsonian syndromes: clinical implications, mechanisms and potential treatments

“…5 Thus, low levels of α-syn expression and correct localization at the postsynaptic region of the NMJ is important for normal muscle function and glucose transport, but high levels and mislocalization of α-syn can lead to muscle wasting and dysfunction. Increased α-syn protein expression was detected in muscles from the methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) mouse model of PD 8 and treatment of C2C12 muscle cells with 1-methyl-4phenylpyridinium increased α-syn protein expression. 9 Furthermore, α-syn expression was identified in extracellular medium from isolated skeletal muscles from aged rats.…”

The Integrated Approach to Inherited Disorders in Neurotransmitters from Molecules to Systems

“…Starting from an initial review of the impairment in the synthesis of dopamine and serotonin due to mutations in the ddc coding for aromatic amino acid decarboxylase (AADC) [1] that lead to severe pathological conditions of infantile parkinsonism, the main focus is on neurodegeneration and Parkinson's disease (PD) as well as the regulation of epilepsy and neuroendocrine cells. Han [2,3] and Seo [4] studied the expression levels of various genes coding for tyrosine hydroxylase, serine/arginine-rich protein-specific kinase 3, and integrin α7 with respect to α-synuclein in SH-SY5Y and C2C12 cells as well as in a PD mouse model. Interestingly, all these proteins were less expressed in cells and the muscles of the mouse model, while α-synuclein expression was increased.…”