AbstractParkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease.

摘要帕金森病（PD）是全球增长最快的神经系统疾病，由于进行性残疾，左旋多巴耐药症状的出现以及与治疗相关的并发症，给管理带来了巨大挑战。在这篇综述中，我们研究了PD疗法的研究现状，并概述了未来促进我们对该疾病的理解和治疗的优先事项。

We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management.

我们确定了未来几年的两个主要研究重点：首先，通过整合敏感的生物标志物和靶向生物疗法来减缓疾病的进展，其次，加强现有的对症治疗，包括手术和输注疗法，目的是延缓并发症和改善长期患者管理。

The path towards disease modification is impeded by the multifaceted pathophysiology and diverse mechanisms underlying PD. Ongoing studies are directed at α-synuclein aggregation, complemented by efforts to address specific pathways associated with the less common genetic forms of the disease. The success of these efforts relies on establishing robust end points, incorporating technology, and identifying reliable biomarkers for early diagnosis and continuous monitoring of disease progression.

PD的多方面病理生理学和多种机制阻碍了疾病修饰的途径。正在进行的研究针对α-突触核蛋白聚集，并辅以解决与较不常见的疾病遗传形式相关的特定途径的努力。这些努力的成功依赖于建立强有力的终点，结合技术，并确定可靠的生物标志物，用于早期诊断和持续监测疾病进展。

In the context of symptomatic treatment, the focus should shift towards refining existing approaches and fostering the development of novel therapeutic strategies that target levodopa-resistant symptoms and clinical manifestations that substantially impair quality of life.Key points.

在对症治疗的背景下，重点应该转向改进现有方法，并促进针对左旋多巴耐药症状和严重损害生活质量的临床表现的新型治疗策略的发展。。

Parkinson disease (PD) is the fastest growing neurological disorder globally but, currently, no therapeutic intervention can modify disease progression and treatment is still based on levodopa (either alone or in combination with dopamine agonists or monoamine oxidase B or catechol-O-methyltransferase inhibitors) and device-aided therapies..

帕金森病（PD）是全球增长最快的神经系统疾病，但目前，没有治疗干预可以改变疾病的进展，治疗仍然基于左旋多巴（单独或与多巴胺激动剂或单胺氧化酶B或儿茶酚-O-甲基转移酶抑制剂）和设备辅助疗法。。

Disease-modifying therapies targeting α-synuclein that are under investigation include active and passive immunization and small molecules that can inhibit protein aggregation.

正在研究的针对α-突触核蛋白的疾病缓解疗法包括主动和被动免疫以及可以抑制蛋白质聚集的小分子。

Studies of compounds that can enhance glucocerebrosidase activity, reduce leucine-rich repeat kinase 2 activity or prevent inflammation are ongoing or starting.

正在进行或正在开始研究可以增强葡萄糖脑苷脂酶活性，降低富含亮氨酸的重复激酶2活性或预防炎症的化合物。

Medications that can alleviate symptomatic manifestations, including new levodopa formulations, dopamine agonists with different dopamine receptor stimulation profiles or modes of administration, and gene and cell transplantation therapies, are under investigation.

。

Early detection of PD is crucial, and educational programmes aimed at the general population could aid this effort by increasing awareness of the early symptoms.

PD的早期发现至关重要，针对普通人群的教育计划可以通过提高对早期症状的认识来帮助这一努力。

Biomarker discovery and validation initially require considerable financial and human resources, but the development of safe, easy-to-perform biomarker assays — for example, using blood samples or skin biopsies — would allow screening of large cohorts in a cost-effective manner.

生物标志物的发现和验证最初需要大量的财政和人力资源，但开发安全，易于执行的生物标志物检测方法-例如，使用血液样本或皮肤活检-将允许以具有成本效益的方式筛选大型队列。

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Fig. 1: Pathophysiological mechanisms underlying Parkinson disease and possible disease-modifying therapies.

图1：帕金森病的病理生理机制和可能的疾病缓解疗法。

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Download referencesAuthor informationAuthors and AffiliationsDepartment of Neurology, University San Raffaele, Rome, ItalyFabrizio StocchiDeptartment of Neurology, Institute for Research and Medical Care, IRCCS San Raffaele, Rome, ItalyFabrizio Stocchi & Daniele BraviCenter for Neurodegenerative Diseases (CESNE), Department of Neuroscience, University of Padova, Padova, ItalyAron Emmi & Angelo AntoniniInstitute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, ItalyAron EmmiParkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, Padua Neuroscience Center (PNC), University of Padova, Padova, ItalyAngelo AntoniniAuthorsFabrizio StocchiView author publicationsYou can also search for this author in.

下载参考文献作者信息作者和所属机构罗马圣拉斐尔大学神经病学系，罗马IRCCS圣拉斐尔研究与医疗保健研究所神经病学系，罗马，意大利法布里齐奥·斯托奇和丹尼尔·布拉维中心神经退行性疾病（CESNE），帕多瓦大学神经科学系，帕多瓦大学神经科学系，伊塔利扬·埃米和安杰洛·安东尼安人体解剖学研究所，帕多瓦大学神经科学系，帕多瓦，伊塔利扬·埃米帕金森和运动障碍科，罕见神经疾病中心（ERN-RND）神经科学，帕多瓦神经科学中心（PNC），帕多瓦大学，帕多瓦，意大利安东尼安·安杰洛作者Fabrizio StocchiView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarDaniele BraviView author publicationsYou can also search for this author in

PubMed Google ScholardanieleBraviview作者出版物您也可以在

PubMed Google ScholarAron EmmiView author publicationsYou can also search for this author in

PubMed Google ScholarAron EmmiView作者出版物您也可以在

PubMed Google ScholarAngelo AntoniniView author publicationsYou can also search for this author in

PubMed Google ScholarAngelo AntoniniView作者出版物您也可以在

PubMed Google ScholarContributionsAll authors researched data for the article and wrote the article. F.S., D.B. and A.A. contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.Corresponding authorCorrespondence to

PubMed谷歌学术贡献所有作者都为这篇文章研究了数据并撰写了这篇文章。F、 S.，D.B.和A.A.对内容的讨论做出了重大贡献，并在提交前审查和/或编辑了稿件。对应作者对应

Fabrizio Stocchi.Ethics declarations

法布里齐奥·斯托奇。道德宣言

Competing interests

相互竞争的利益

F.S. has received compensation for consultancy and speaker-related activities from UCB, Britannia, AbbVie, Zambon, Bial, Ever Pharma, Synegile, Biogen, Roche, Blue Rock, Chiesi Pharmaceuticals, Lundbeck, Sunovion and Kiowa. D.B. is a business partner of SixDegrees HealthCare and has received fees from Clexio, Herantis, Theravance, Novartis and PPD.

F、 美国已从UCB、Britannia、AbbVie、Zambon、Bial、Ever Pharma、Synegile、Biogen、Roche、Blue Rock、Chiesi Pharmaceuticals、Lundbeck、Sunovion和Kiowa获得咨询和演讲相关活动的报酬。D、 B.是SixDegrees HealthCare的商业合作伙伴，曾从Clexio、Herantis、Theravance、Novartis和PPD收取费用。

A.A. has received compensation for consultancy and speaker-related activities from UCB, Britannia, AbbVie, Zambon, Bial, Ever Pharma, Ferrer, Theravance Biopharma, Bayer, TreeFrog Therapeutics, Oligy and Medscape. He receives research support from Lundbeck, Bial, Movement Disorders Society, Horizon2020 Grant 825785, Horizon2020 Grant 101016902, Ministry of Education University and Research (MIUR) Grant ARS01_01081 and Fondazione Grigioni per la Malattia di Parkinson.

A、 A.已从UCB、Britannia、AbbVie、Zambon、Bial、Ever Pharma、Ferrer、Theravance Biopharma、Bayer、TreeFrog Therapeutics、Oligy和Medscape获得咨询和演讲相关活动的报酬。他获得了运动障碍协会Lundbeck，Bial，Horizon2020 Grant 825785，Horizon2020 Grant 101016902，教育部大学和研究（MIUR）Grant ARS01\U 01081和Fondazione Grigioni per la Malattia di Parkinson的研究支持。

A.E. declares no competing interests..

A、 E.宣布没有利益冲突。。

Peer review

同行评审

Peer review information

同行评审信息

Nature Reviews Neurology thanks D. Nyholm, who co-reviewed with M. Öthman; A. Cenci; N. Hattori; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

自然评论神经病学感谢D.Nyholm，他与M.Öthman共同评论；A、 Cenci公司；N、 服部；另一位匿名审稿人对这项工作的同行评审做出了贡献。

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Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。权利和许可Pringer Nature或其许可人（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Stocchi，F.，Bravi，D.，Emmi，A。

et al. Parkinson disease therapy: current strategies and future research priorities..

帕金森病治疗：当前策略和未来研究重点。。

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