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Horino, T., Ito, H., Yamaguchi, T., Furihata, M. and Hashimoto, K. (2005) Suppressive effects of iron on TGF-beta1 production by renal proximal tubular epithelial cells. Nephron Experimental Nephrology, 100, e1-e10.


  • 标题: 假说:TGF-β1/Smad3信号通路参与帕金森病的发生发展A Hypothesis: TGF-β1/Smad3 Signaling Pathway Participates in the Development of Parkinson’s Disease

    作者: 于永鹏

    关键字: 帕金森病, , 转化生长因子-β1, 6-羟基多巴胺Parkinson’s Disease, Iron, TGF-β1, 6-Hydroxydopamine

    期刊名称: 《Open Journal of Nature Science》, Vol.3 No.2, 2015-05-26

    摘要: 帕金森病(Parkinson’s disease, PD)是严重威胁人类健康的神经变性疾病之一,迄今没有特殊有效的治疗方法。脑铁代谢紊乱及其介导的氧化应激反应与PD发病关系密切,但其调节机制尚不明确。新近发现,转化生长因子(Transforming growth factor-β1, TGF-β1)能下调铁蛋白重链(Ferritin heavy chain, FHC)的表达并导致细胞易变铁库增加,在血色素沉着病研究中发现TGF-β1/Smads信号通路通过调节铁调素(Hepcidin, Hep)的表达调控细胞铁代谢。本文重点论述TGF-β1/Smads信号通路参与铁代谢及氧化应激调控的可能机制,并提出医学假说:TGF-β1/Smad3信号通路参与PD的发生发展过程。希望将来能以TGF-β1/Smad3信号通路为切入点,探讨该通路的异常调控对PD脑铁代谢相关蛋白表达及铁水平的影响,并探讨TGF-β1信号对多巴胺能神经元氧化应激调控的机制,这对揭示PD发病机制、寻找有效的治疗方法具有重要意义。 Parkinson’s disease (PD), which is one of neurodegenerative diseases, is a serious threat to human health. So far there has been no special treatment for it. PD onset is closely associated with the disorders of iron metabolism and its inducing and mediating oxidative stress response in the brain. The mechanism of its regulation is still elusive. Recently it was found that transforming growth factor-β1 (TGF-β1) can down-regulate the expression of ferritin heavy chain (FHC) and lead to cell labile iron increasing. It was found that TGF-β1/Smads signaling pathway could regulate cellular iron transport and metabolic balance by regulating hepcidin (Hep) expression in the hemochromatosis research. This review focused on the possible mechanism of TGF-β1/Smads signaling pathway involving iron metabolism and oxidative stress regulation and proposed a medical hypothesis: TGF-β1/Smad3 signaling pathway might participate in the process of PD de-velopment. It is expected that the experiment will be performed to explore the effect of abnormal regulation of this signaling pathway on the iron metabolism protein expressions and iron levels in PD, and to investigate regulatory mechanism of the TGF-β1 signaling on oxidative stress in dopa-minergic neurons. It will be of great significance to reveal the mechanism of PD, and to find effective treatments for it.