国内团队:小檗碱或可调节肠脑轴以治疗帕金森病
创作:菌菌君 审核:szx 03月05日
  • 帕金森病(PD)小鼠移植粪肠球菌或屎肠球菌,可增加大脑多巴胺水平并改善PD症状,小檗碱(BBR)联合细菌治疗效果优于单独细菌治疗;
  • 口服肠球菌属可提升小鼠大脑纹状体中的多巴胺水平,而BBR可进一步增加大脑中的多巴胺水平;
  • BBR是肠球菌属的酪氨酸羟化酶的激动剂,以促进肠道中的左旋多巴产生;
  • 28例高脂血症患者的临床研究证实,口服BBR可通过肠道细菌增加血液/粪便中的左旋多巴水平。
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szx
酪氨酸羟化酶是产生左旋多巴的限速酶。中国医学科学院药物研究所的蒋建东团队、王琰团队及中国医学科学院基础医学研究所的曹雪涛团队在Signal Transduction and Targeted Therapy上发表的一项最新研究,发现在帕金森病(PD)小鼠模型中,口服小檗碱(BBR)可通过增强肠球菌属的酪氨酸羟化酶活性,促进肠道中的左旋多巴产生,从而增加大脑中的多巴胺水平,以改善PD症状,在临床研究中也有相似发现。
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Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

口服小檗碱通过调节肠道菌群以提高大脑多巴胺,从而改善帕金森病

10.1038/s41392-020-00456-5

02-24, Article

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The phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.

First Authors:
Yan Wang,Qian Tong,Shu-Rong Ma,Zhen-Xiong Zhao

Correspondence Authors:
Yan Wang,Xuetao Cao,Jian-Dong Jiang

All Authors:
Yan Wang,Qian Tong,Shu-Rong Ma,Zhen-Xiong Zhao,Li-Bin Pan,Lin Cong,Pei Han,Ran Peng,Hang Yu,Yuan Lin,Tian-Le Gao,Jiawen Shou,Xiao-Yang Li,Xian-Feng Zhang,Zheng-Wei Zhang,Jie Fu,Bao-Ying Wen,Jin-Bo Yu,Xuetao Cao,Jian-Dong Jiang

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