Decrease in ITGA7 Levels Is Associated with an Increase in α-Synuclein Levels in an MPTP-Induced Parkinson’s Disease Mouse Model and SH-SY5Y Cells

Abstract

We investigated the potential association between integrin α7 (ITGA7) and alpha-synuclein (α-syn) in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model. Tyrosine hydroxylase (TH), ITGA7, and α-syn expression in the substantia nigra (SN) of the brain were observed to examine the pathological characteristics of PD. To determine the relationship between ITGA7 and PD, the expression of TH and α-syn was investigated after ITGA7 siRNA knockdown in SH-SY5Y cells. The ITGA7 microarray signal was decreased in the SN of the MPTP group, indicating reduced ITGA7 expression compared to that in the control. The expression patterns of ITGA7 in the control group and those of α-syn in the MPTP group were similar on immunohistochemical staining. Reduction in ITGA7 expression by ITGA7 siRNA administration induced a decrease in TH expression and an increase in α-syn expression in SH-SY5Y cells. The decreased expression of ITGA7 significantly decreased the expression of bcl2 and increased the bax/bcl2 ratio in SH-SY5Y cells. These results suggest that reduced ITGA7 expression may be related to increased α-syn expression and apoptosis of dopaminergic cells in an MPTP-induced PD mouse model. To the best of our knowledge, this is the first study to show an association between ITGA7 and PD.

Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis

“…TGA7, one of miR-615-5p’s targets, is known as a cell surface receptor for laminin-1 that mediates ECM adhesion and regulates various cellular processes ( 23 ). A study investigated that inhibition of ITGA7 down-regulated the expression of BCL2 and increased the BAX/BCL2 ratio, causing apoptosis of SH-SY5Y cells in Parkinson’s disease mouse models ( 24 ). The other ECM protein COL6A1 that targeted by miR-1233-3p, was mostly found on the close periphery of the cell surface and considered a neuroprotective role against the toxicity of amyloid-β peptides in Alzheimer’s disease mouse models ( 25 ).…”

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

“…Given the association between ITGA7 and myopathy, ITGA7 might be potentially linked with the muscle in PD, considering the motor symptoms. In a previous study [ 14 ], which reduced ITGA7 expression can be associated with enhanced α-syn in the brain of MPTP-induced mice. In addition, we postulated that muscle ITGA7 expression is altered during PD.…”

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.…”