Ho Dong Hwan, Kim Hyejung, Nam Daleum, Seo Mi Kyoung, Park Sung Woo, Kim Dong-Kyu, Son Ilhong
InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, 321, Sanbon-ro, Gunpo-si 15865, Republic of Korea;
Paik Institute for Clinical Research, Inje University College of Medicine, Busan-si 47392, Republic of Korea;
NeuroSci. 2024 Aug 30;5(3):301-314. doi: 10.3390/neurosci5030024. eCollection 2024 Sep.
Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are involved in the pathogenesis of Parkinson's disease. The activity of LRRK2 in microglial cells is associated with neuroinflammation, and LRRK2 inhibitors are crucial for alleviating this neuroinflammatory response. α-synuclein contributes to oxidative stress in the dopaminergic neuron and neuroinflammation through Toll-like receptors in microglia. In this study, we investigated the effect of the marine alga on neuroinflammation by examining LRRK2 activation and the aggregation of α-synuclein. extract inhibits LRRK2 activity in vitro and decreases lipopolysaccharide (LPS)-induced LRRK2 upregulation in BV2, a mouse microglial cell line. Treatment with extract decreased tumor necrosis factor-α (TNF-α) gene expression by LPS through LRRK2 inhibition in BV2. It also attenuated TNF-α gene expression, inducible nitric oxide synthase, and the release of TNF-α and cellular nitric oxide in rat primary microglia. Furthermore, extract prevented rotenone (RTN)-induced oxidative stress in primary rat astrocytes and inhibited α-synuclein fibrilization in an in vitro assay using recombinant α-synuclein and in the differentiated human dopaminergic neuronal cell line SH-SY5Y (dSH). The extract increased lysosomal activity in dSH cells. In addition, extract slightly prolonged the lifespan of , which was reduced by RTN treatment.
富含亮氨酸重复激酶2(LRRK2)和α-突触核蛋白参与帕金森病的发病机制。小胶质细胞中LRRK2的活性与神经炎症相关,LRRK2抑制剂对于减轻这种神经炎症反应至关重要。α-突触核蛋白通过小胶质细胞中的Toll样受体导致多巴胺能神经元的氧化应激和神经炎症。在本研究中,我们通过检测LRRK2激活和α-突触核蛋白聚集来研究海藻对神经炎症的影响。海藻提取物在体外抑制LRRK2活性,并降低脂多糖(LPS)诱导的小鼠小胶质细胞系BV2中LRRK2的上调。用海藻提取物处理通过抑制BV2中的LRRK2降低了LPS诱导的肿瘤坏死因子-α(TNF-α)基因表达。它还减弱了大鼠原代小胶质细胞中TNF-α基因表达、诱导型一氧化氮合酶以及TNF-α和细胞一氧化氮的释放。此外,海藻提取物在原代大鼠星形胶质细胞中预防了鱼藤酮(RTN)诱导的氧化应激,并在使用重组α-突触核蛋白的体外试验以及分化的人多巴胺能神经元细胞系SH-SY5Y(dSH)中抑制了α-突触核蛋白纤维化。该提取物增加了dSH细胞中的溶酶体活性。此外,海藻提取物略微延长了经RTN处理后缩短的线虫寿命。