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首页> 外文期刊>Mechanisms of Ageing and Development >Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice
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Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice

机译：多靶铁螯合剂M30对小鼠年龄相关性改变的神经保护

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摘要

Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we report that a chronic systemic treatment of aged mice with M30 (1 and 5. mg/kg; 4 times weekly for 6 months), had a significant positive impact on neuropsychiatry functions and cognitive age-related impairment. M30 significantly reduced cerebral iron accumulation as demonstrated by Perl's staining, accompanied by a marked decrease in cerebral β-amyloid plaques. In addition, our results demonstrate that M30 caused a significant inhibition of both MAO-A and -B activities in the cerebellum of aged mice, compared with vehicle-treated aged control mice. In summary, the present study indicates that the novel MAO inhibitor/iron chelating drug, M30, acting against multiple brain targets could reverse age-associated memory impairment and provide a potential treatment against the progression of neurodegeneration in ageing.
机译：基于多模式药物设计范例，我们合成了多功能，无毒，可透脑的铁螯合化合物M30，具有抗帕金森病药物的神经保护性N-炔丙基部分，单胺氧化酶（MAO）-B抑制剂，雷沙吉兰和铁螯合剂VK28的8-羟基喹啉衍生物的抗氧化剂-铁螯合剂部分。在这里，我们报道了M30（1和5. mg / kg;每周4次，共6个月）对老年小鼠的慢性全身治疗，对神经精神病学功能和与认知年龄相关的损伤具有明显的积极影响。如Perl染色所示，M30显着降低了脑铁的蓄积，并伴有脑β-淀粉样斑块的明显减少。此外，我们的研究结果表明，与媒介物治疗的老年对照小鼠相比，M30对老年小鼠小脑的MAO-A和-B活性均具有显着抑制作用。总而言之，本研究表明，针对多个脑靶的新型MAO抑制剂/铁螯合药物M30可以逆转与年龄相关的记忆障碍，并为对抗衰老中神经退行性疾病的发展提供潜在的治疗方法。

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