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一种大蒜化合物对帕金森病中星形胶质细胞介导的神经炎症的预防作用。

Preventive effect of a garlic compound on astrocyte-mediated neuroinflammation in Parkinson's disease.

作者信息

Seol Jaeheon, Kim Jaehoon, Moon Sung Min, Jung Duwon, Kang Changyu, Chung Ki Wung, Jung Young-Suk, Chung Young-Hwa, Jung Yunjin, Chung Hae Young, Chang Seung-Cheol, Lee Jaewon

机构信息

College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea; Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.

College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea; Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.

出版信息

Neuropharmacology. 2025 Sep 1;275:110494. doi: 10.1016/j.neuropharm.2025.110494. Epub 2025 May 3.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and resultant severe motor dysfunction. While current treatments primarily focus on maintaining dopamine levels, effective targeting of neuroinflammation, an important driver of disease progression, remains an unmet need. This study investigates the neuroprotective potential of BMDA (BMDA(N-benzyl-N-methyldecan-1-amine)), a natural compound derived from garlic with strong anti-inflammatory properties, using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD. Behavioral assessments, immunohistochemistry, and dopamine analysis showed that BMDA effectively reduced neuroinflammation and preserved dopaminergic neurons. In vitro studies showed that BMDA significantly suppressed inflammatory markers and reduced astrocyte activation in MPP-induced primary cultured astrocytes, and real-time PCR confirmed that BMDA attenuated proinflammatory cytokines and chemokines. Further mechanistic studies showed that BMDA inhibited the p-p65 and p-ERK signaling pathways, which underlie astrocyte-mediated neuroinflammation. These findings suggest that BMDA should be considered a therapeutic candidate for PD that targets neuroinflammation.

摘要

帕金森病(PD)是一种进行性神经退行性疾病,其特征为多巴胺能神经元丧失以及由此导致的严重运动功能障碍。虽然目前的治疗主要集中在维持多巴胺水平,但有效靶向神经炎症(疾病进展的一个重要驱动因素)仍然是一个未满足的需求。本研究使用MPTP(1-甲基-4-苯基-1,2,3,6-四氢吡啶)诱导的PD小鼠模型,研究了BMDA(BMDA(N-苄基-N-甲基癸-1-胺))的神经保护潜力,BMDA是一种从大蒜中提取的具有强大抗炎特性的天然化合物。行为评估、免疫组织化学和多巴胺分析表明,BMDA有效减轻了神经炎症并保护了多巴胺能神经元。体外研究表明,BMDA显著抑制了MPP诱导的原代培养星形胶质细胞中的炎症标志物并减少了星形胶质细胞的激活,实时PCR证实BMDA减弱了促炎细胞因子和趋化因子。进一步的机制研究表明,BMDA抑制了p-p65和p-ERK信号通路,而这两条信号通路是星形胶质细胞介导的神经炎症的基础。这些发现表明,BMDA应被视为一种针对神经炎症的PD治疗候选药物。

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