5-α 还原酶抑制剂对帕金森病动物模型的影响。

IF 6.5 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology Pub Date : 2024-10-01 DOI:10.1016/j.yfrne.2024.101156

Mélanie Bourque , Marc Morissette , Amandine Isenbrandt , Silvia Giatti , Roberto Cosimo Melcangi , Manolo Carta , Roberto Frau , Marco Bortolato , Denis Soulet , Thérèse Di Paolo

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引用次数: 0

摘要

帕金森病（Parkinson's disease，PD）的特征是因大脑多巴胺丧失而出现运动症状和非运动症状，包括胃肠功能紊乱。虽然帕金森病无法治愈，但可以对症治疗。左旋多巴是治疗帕金森氏症的金标准，但大多数患者会出现运动障碍（LID），难以控制。金刚烷胺被认为是治疗运动障碍最有效的药物，但其不良反应限制了它在患者中的使用。在此，我们回顾了用于治疗良性前列腺增生和脱发的 5α 还原酶抑制剂（5ARIs）是如何在帕金森氏症动物模型中显示出有益作用的。5ARIs 对大脑和肠道多巴胺能系统具有神经保护作用，并能减少啮齿类动物模型中的运动障碍。此外，5ARI 非那雄胺还能抑制帕金森病患者由多巴胺能引起的药物赌博。5ARIs在帕金森病动物模型中的神经保护和抗运动障碍活性表明，它们有可能被重新用于男性帕金森病患者，以解决肠道功能障碍、保护大脑多巴胺并抑制运动障碍。

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Effect of 5-alpha reductase inhibitors in animal models of Parkinson’s disease

Parkinson’s disease (PD) is characterized by motor symptoms due to loss of brain dopamine and non-motor symptoms, including gastrointestinal disorders. Although there is no cure for PD, symptomatic treatments are available. L-Dopa is the gold standard PD therapy, but most patients develop dyskinesias (LID), which are challenging to manage. Amantadine is recognized as the most effective drug for LID, but its adverse effects limit the use in patients. Here we review how 5α-reductase inhibitors (5ARIs), drugs used to treat benign prostatic hyperplasia and alopecia, exhibit beneficial effects in PD animal models. 5ARIs show neuroprotective properties in brain and gut dopaminergic systems, and reduce dyskinesias in rodent model of PD. Additionally, the 5ARI finasteride dampened dopaminergic-induced drug gambling in PD patients. Neuroprotection and antidyskinetic activities of 5ARIs in animal models of PD suggest their potential repurposing in men with PD to address gut dysfunction, protect brain DA and inhibit dyskinesias.

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来源期刊

Frontiers in Neuroendocrinology 医学-内分泌学与代谢

CiteScore

13.30

自引率

6.80%

发文量

审稿时长

68 days

期刊介绍： Frontiers in Neuroendocrinology (FIN) publishes a wide range of informative articles including comprehensive reviews, systematic reviews, opinion pieces, and meta-analyses. While the majority of reviews are invited, we also embrace unsolicited reviews and meta-analyses, as well as proposals for thematic special issues, provided they meet our rigorous quality standards. In addition, we encourage authors to submit commentaries that concisely present fresh ideas or offer further analysis to delve deeper into the implications of an article published in our journal.