College of Korean Medicine, Sangji University, #83 Sangjidae-Gil, Wonju, Gangwon-Do, 26339, Republic of Korea.
WHO Collaborating Center for Traditional Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul, 02447, Republic of Korea.
BMC Neurosci. 2021 Nov 4;22(1):65. doi: 10.1186/s12868-021-00668-7.
Parkinson's disease (PD) represent a loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain. However, its cause remains unknown and Triadin (TRDN) function in the brain is also unknown. To examine the relationship between TRDN and PD, the expression levels of protein related to PD in TRDN knockdown status were studied in the SH-SY5Y cells. Cell viability and apoptosis were assessed to examine the apoptosis effect on dopaminergic cells by decreased TRDN, and the levels of the proteins related to apoptosis were also confirmed.
This study confirmed decreased TRDN expression level (P < 0.005) at the SN in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model and identified the functional features of TRDN. Our results showed a relationship between TRDN expression and PD in that reduced TRDN level induced PD-like characteristics. Interestingly, there was TRDN expression in the regions where dopaminergic cells are in the SN, and the expression patterns of TRDN and tyrosine hydroxylase (TH) were similar. Decreased TRDN level also induced apoptotic characteristics and the Fluorescence-activated cell sorting analysis results showed that apoptosis increased (P < 0.05) as the TRDN small interfering RNA concentration increased. The cytotoxicity assay revealed that cell viability also decreased (P < 0.0005) in the same condition as that in the Fluorescence-activated cell sorting analysis.
Decreased TRDN level could be related with the apoptotic death of dopaminergic cells at the SN in PD, and TRDN administration could give a positive effect on PD by reducing apoptotic cell death.
帕金森病（PD）代表中脑黑质（SN）中的多巴胺能神经元丧失。然而，其病因仍不清楚，Triadin（TRDN）在大脑中的功能也不清楚。为了研究 TRDN 与 PD 之间的关系，在 SH-SY5Y 细胞中研究了 TRDN 敲低状态下与 PD 相关的蛋白表达水平。评估细胞活力和细胞凋亡，以研究通过降低 TRDN 对多巴胺能细胞的凋亡作用，并确认与凋亡相关的蛋白水平。
本研究在 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的 PD 小鼠模型中证实了 SN 中 TRDN 表达水平降低（P<0.005），并确定了 TRDN 的功能特征。我们的研究结果表明，TRDN 表达与 PD 之间存在关系，即降低 TRDN 水平可诱导 PD 样特征。有趣的是，TRDN 在 SN 中多巴胺能细胞存在的区域表达，并且 TRDN 和酪氨酸羟化酶（TH）的表达模式相似。降低 TRDN 水平还诱导了凋亡特征，荧光激活细胞分选分析结果表明，随着 TRDN 小干扰 RNA 浓度的增加，凋亡增加（P<0.05）。细胞毒性测定显示，在与荧光激活细胞分选分析相同的条件下，细胞活力也降低（P<0.0005）。
TRDN 水平降低可能与 PD 中 SN 中多巴胺能细胞的凋亡性死亡有关，TRDN 给药可通过减少凋亡性细胞死亡对 PD 产生积极影响。
