Chang Wan-Hsuan, Hsu Hung-Te, Lin Chih-Cheng, An Li-Mei, Lee Chien-Hsing, Ko Horng-Huey, Lin Chih-Lung, Lo Yi-Ching
Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2024 Feb 21;25(5):2514. doi: 10.3390/ijms25052514.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABA-α1), and γ-Aminobutyric acid type B (GABA). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.
帕金森病（PD）是一种常见的神经退行性疾病，其特征是黑质致密部（SNpc）中的多巴胺能神经元逐渐丧失，导致纹状体中多巴胺水平降低，最终出现运动症状。芳樟醇（3,7 - 二甲基 - 1,6 - 辛二烯 - 3 - 醇）是芳香植物中的一种单萜，具有抗氧化、抗抑郁和抗焦虑特性。本研究的目的是评估芳樟醇对经1 - 甲基 - 4 - 苯基吡啶离子（MPP）处理的多巴胺能SH - SY5Y细胞、原代中脑和皮质神经元，以及由1 - 甲基 - 4 - 苯基 - 1,2,3,6 - 四氢吡啶（MPTP）诱导的帕金森病样小鼠的神经保护作用。进行了细胞活力、α - 微管蛋白染色、蛋白质印迹、免疫组织化学和行为实验。在经MPP处理的SH - SY5Y细胞中，芳樟醇提高了细胞活力，减少了神经突回缩，通过下调凋亡信号（B细胞淋巴瘤2（Bcl - 2）、裂解的半胱天冬酶 - 3和聚ADP - 核糖聚合酶（PARP））和吞噬细胞NADPH氧化酶（gp91）增强了抗氧化防御，以及通过上调神经营养信号（脑源性神经营养因子（BDNF）和神经生长因子（NGF））和核因子红细胞2相关因子2（Nrf2）/血红素加氧酶 - 1（HO - 1）途径。在经MPP处理的原代中脑神经元中，芳樟醇增强了酪氨酸羟化酶（TH）、沉默调节蛋白1（SirT1）和帕金蛋白的表达。在经MPP处理的原代皮质神经元中，芳樟醇上调了SirT1、γ - 氨基丁酸A型α1（GABA - α1）和γ - 氨基丁酸B型（GABA）的蛋白表达。在帕金森病样小鼠中，芳樟醇减轻了SNpc中多巴胺能神经元的损失。芳樟醇改善了帕金森病样小鼠的运动和非运动行为缺陷以及肌肉力量。这些发现表明芳樟醇可能保护多巴胺能神经元并改善帕金森病的损伤症状。
