INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Linwei Yu,Xi Li,Tianyi Shi,Ning Li,Donge Zhang,Xikai Liu,Yushuo Xiao,Xinran Liu,Robert B. Petersen,Weikang Xue,Yanxun V. Yu,De-sheng Hu,Li Xu,Hong Chen,Ling Zheng,Kun Huang,Anlin Peng
Parkinson's disease (PD), a neurodegenerative disorder without cure, is characterized by the pathological aggregation of α-synuclein (α-Syn) in Lewy bodies. Classic deposition pathway and condensation pathway contribute to α-Syn aggregation, and liquid-liquid phase separation is the driving force for condensate formation, which subsequently undergo liquid-solid phase separation to form toxic fibrils. Traditional Chinese Medicine (TCM) has a long history in treating neurodegenerative disease; herein, we identified chemicals from herbs that inhibit α-Syn aggregation. We screened commonly prescribed TCMs for PD from the CNKI database and registered patents, 13 chemicals were identified in the TCMSP databases as candidate inhibitors, among which three phenols, forsythoside B (FTSB), echinacoside (ECH), and 4-hydroxyindole (C4-OH) efficiently inhibit α-Syn aggregation. Moreover, FTSB and ECH increase α-Syn fluidity within condensates, inhibit α-Syn transition into amyloid fibrils and reduce fibril-induced toxicity in SH-SY5Y cells. Importantly, they disaggregated preformed α-Syn amyloid fibrils. Notably, in an α-Syn overexpressing NL5901 C. elegans PD model, either FTSB or ECH treatment significantly extended the lifespan and improved the PD-like movement disorders, both in the preventive and therapeutic treatment approaches, by reducing toxic α-Syn inclusion formation and improving the fluidity of α-Syn. Together, we offer new therapeutic candidates targeting phase separation-associated aggregation for PD.
研究领域:
神经科学
·
药理学
·
分子生物学
·
传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Likun Yan,Xiao Zhang,Jie Fu,Qiang Liu,Xiaohua Lei,Zhenyu Cao,Ju Zhang,Yaoli Shao,Qing Tong,Wei Qin,Xinxu Liu,Chun Liu,Zhiqiang Liu,Zhenghao Li,Jueliang Lu,Xundi Xu
Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl 4 -induced hepatic fibrosis mouse model. The TRPV3 selective agonist drofenine and its inhibitor, forsythoside B, were intraperitoneally injected to investigate the relationship between TRPV3 and liver fibrosis progression. Finally, in vitro studies were performed using hepatic stellate cells (HSCs) to discover the potential molecular biological mechanisms. Immunohistochemistry revealed TRPV3 overexpression in liver cirrhosis. In the liver fibrosis groups, TRPV3 inhibitor treatment significantly reduced liver fibrosis, while TRPV3 agonist exacerbated its progression. In HSCs, knocking down TRPV3 with siRNA impaired DNA synthesis and cell proliferation and increased cell apoptosis. Furthermore, we found that knockdown of TRPV3 could reduce the lectin like oxidized lowdensity lipoprotein receptor-1 (LOX-1) protein levels. Our research suggests that lower expression or functional levels of TRPV3 can ameliorate the inflammatory response and fibrotic tissue proliferation.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）