英国曼彻斯特大学研究人员发现，从大豆中提取的名为染料木黄酮的物质，可帮助治疗粘多糖贮积症，这种疾病会导致儿童痴呆和夭折。
粘多糖贮积症是一种遗传疾病，新生儿由于基因存在缺陷而缺少相应的酶，导致糖分无法分解而在大脑中堆积，最终使神经功能受损，出现痴呆、行为异常等，孩子在十几岁就夭折。
本次研究发现，患病实验鼠在服用大剂量的染料木黄酮9个月后，大脑中多余的糖分减少了三分之一，神经系统功能的退化速度减慢，并不再出现这种疾病导致的行为异常。
研究人员布雷恩比格说，粘多糖贮积症目前还没有很好的治愈方法。研究小组将在本次实验的基础上开展人类临床研究，探索治疗这种疾病的新途径。
相关研究成果发表在新一期《公共科学图书馆―综合》（Public Library of Science One）杂志上。
推荐原文出处：
PLoS ONE, DOI: 10.1371/journal.pone.0014192
Genistein Improves Neuropathology and Corrects Behaviour in a Mouse Model of Neurodegenerative Metabolic Disease
Marcelina Malinowska1,2#, Fiona L. Wilkinson1#, Kia J. Langford-Smith1, Alex Langford-Smith1, Jillian R. Brown3, Brett E. Crawford3, Marie T. Vanier4, Grzegorz Grynkiewicz5, Rob F. Wynn6, J. Ed Wraith7, Grzegorz Wegrzyn2, Brian W. Bigger1,6*
1 Mucopolysaccharidosis (MPS) Stem Cell Research Group, Biomedicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom, 2 Department of Molecular Biology, Faculty of Biology, University of Gdansk, Gdansk, Poland, 3 Zacharon Pharmaceuticals Inc., San Diego, California, United States of America, 4 Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 820, Lyon University, Lyon, France, 5 Pharmaceutical Research Institute, Warsaw, Poland, 6 Bone Marrow Transplant Unit, Royal Manchester Children's Hospital, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom, 7 Genetic Medicine, St. Mary's Hospital, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
Background
Neurodegenerative metabolic disorders such as mucopolysaccharidosis IIIB (MPSIIIB or Sanfilippo disease) accumulate undegraded substrates in the brain and are often unresponsive to enzyme replacement treatments due to the impermeability of the blood brain barrier to enzyme. MPSIIIB is characterised by behavioural difficulties, cognitive and later motor decline, with death in the second decade of life. Most of these neurodegenerative lysosomal storage diseases lack effective treatments. We recently described significant reductions of accumulated heparan sulphate substrate in liver of a mouse model of MPSIIIB using the tyrosine kinase inhibitor genistein.
Methodology/Principal Findings
We report here that high doses of genistein aglycone, given continuously over a 9 month period to MPSIIIB mice, significantly reduce lysosomal storage, heparan sulphate substrate and neuroinflammation in the cerebral cortex and hippocampus, resulting in correction of the behavioural defects observed. Improvements in synaptic vesicle protein expression and secondary storage in the cerebral cortex were also observed.
Conclusions/Significance
Genistein may prove useful as a substrate reduction agent to delay clinical onset of MPSIIIB and, due to its multimodal action, may provide a treatment adjunct for several other neurodegenerative metabolic diseases.
