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.
Highlights
As life expectancy and the prevalence of degenerative brain diseases increase, the number of patients with Parkinson’s disease (PD), the second most common degenerative brain disease after Alzheimer’s disease, is increasing rapidly [1]
The major histopathological feature of PD is the deposition of Lewy bodies, and the major protein component of these intracellular deposits is a fibrillar aggregate of α-synuclein (α-syn) [4]
Ca2+ or bax-mediated cytochrome C release, a decrease in bcl2 plays an important role in inducing apoptosis [35]. These results suggest that the decreased expression of ITGA7 could be associated with the increased expression of α-syn and apoptosis of dopaminergic cells
Summary
As life expectancy and the prevalence of degenerative brain diseases increase, the number of patients with Parkinson’s disease (PD), the second most common degenerative brain disease after Alzheimer’s disease, is increasing rapidly [1]. The main symptoms of PD are motor function-related symptoms, including slow movement, tremor, rigidity, and postural instability [2]. The major histopathological feature of PD is the deposition of Lewy bodies, and the major protein component of these intracellular deposits is a fibrillar aggregate of α-synuclein (α-syn) [4]. Increased expression of α-syn was observed in both patients with PD and PD animal models and is reported to be closely related to PD pathology [5]. Self-aggregation of these proteins leads to the formation of an amphipathic helical structure, which may result in membrane association [6]
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