帕金森病精准运动干预的多维体系:基于遗传分型、运动亚型、临床分期和可穿戴数字生物标志物的动态调控
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1)山东体育学院研究生教育学院,济南 250102;2)上海体育大学运动健康学院,上海 200438

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泰山学者工程(tstp20250540)资助项目。


Multidimensional System of Precision Exercise Interventions for Parkinson’s Disease: Dynamic Regulation Based on Genetic Typing, Motor Subtypes, Clinical Staging, and Wearable Digital Biomarkers
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Affiliation:

1)College of Graduate Education, Shandong Sport University, Jinan 250102, China;2)School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China

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This work was supported by a grant from Shandong Taishan Scholar Distinguished Expert Project (tstp20250540).

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    摘要:

    帕金森病(Parkinson’s disease,PD)是全球第二大神经退行性疾病,具有高度的临床、遗传及治疗反应异质性。传统运动疗法虽能通过调控α突触核蛋白聚集、增强线粒体自噬、抑制神经炎症等机制改善运动与非运动症状,但其疗效存在显著的个体差异。这种差异源于内源性因素(如遗传背景、临床表型及疾病分期)与外源性因素(如运动类型、强度与频率)的共同作用。为此,本综述首先从流行病学负担、发病机制异质性和干预反应差异3个方面,论证了对PD患者实施精准运动干预的必要性。继而,本文系统阐述了如何构建精准运动干预策,即依据遗传特征、临床表型与疾病分期进行患者分层,并融合技术辅助工具。在遗传层面,GBA1PRKNPINK1SNCA等基因突变分别导致不同的分子病理,因而需要针对性的运动方案。在临床表型上,需根据震颤主导型与姿势不稳/步态障碍型患者的特征制定目标。此外,干预策略应随疾病进展动态调整,早期以高强度运动为主,提升神经可塑性,中、晚期则分别侧重于功能维持、跌倒预防与代偿策略。最后,本文详述了运动类型、强度、频率等运动参数的个性化配置。本综述提出的PD精准运动干预理论框架,通过整合遗传、表型与分期特征进行患者分层,并利用数字技术实现动态个性化调节,旨在推动运动疗法成为更强效、个体化的精准策略。

    Abstract:

    Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, presents significant heterogeneity in clinical manifestations, genetic background, and response to interventions. While conventional exercise therapies demonstrate benefits in alleviating motor and non-motor symptoms through mechanisms such as modulating α-synuclein aggregation, enhancing mitophagy, and reducing neuroinflammation, their efficacy varies considerably among individuals. This variability may stem from endogenous factors such as genetic background, clinical phenotypes, stages of pathological progression, as well as exogenous factors like the type, intensity, and frequency of movement. Thus, this review first discusses the necessity of precise exercise interventions for PD patients, focusing on the epidemiological burden, heterogeneity in disease mechanisms, and differences in intervention response (Why). Next, we systematically explain how to develop precise exercise intervention strategies by stratifying interventions based on genetic background, clinical phenotype, and disease stage, combined with technological aids (How). Genetically, mutations in genes such as GBA1, PRKN, PINK1, and SNCA dictate distinct molecular pathologies—including lysosomal dysfunction, impaired mitophagy, and α-synuclein aggregation—which necessitate tailored exercise regimens. For instance, patients with PRKN/PINK1 mutations may benefit from moderate-intensity endurance training to support mitochondrial biogenesis without exacerbating oxidative stress, whereas carriers of GBA1 mutations might require exercises focusing on enhancing lysosomal function and managing oxidative damage. Clinically, patients are stratified into tremor-dominant (TD) and postural instability/gait difficulty (PIGD) subtypes, which demand divergent exercise priorities: coordinative, rhythm-based activities like dance or Tai Chi for TD-PD to engage cerebellar circuits, versus targeted balance and strength training, potentially aided by virtual reality, for PIGD-PD to mitigate axial symptoms and fall risk. Furthermore, intervention strategies must evolve with disease progression: high-intensity exercise is prioritized in early stages to leverage neuroplasticity and potential disease modification, while mid- and late-stage management focuses on functional maintenance, fall prevention, and compensatory strategies, respectively. Critical to implementing this framework is the adoption of digital biomarkers via wearable technology (e.g., inertial sensors, smartwatches), which enables continuous, objective monitoring of gait, tremor, and physiological responses. This facilitates a closed-loop feedback system, allowing for the remote adjustment of exercise parameters (intensity, frequency, duration) in real-time, thus optimizing efficacy and ensuring safety. Finally, we detail how to configure exercise parameters through personalized adaptation (What), including exercise type, intensity, frequency and dose. Higher volumes of physical activity are associated with reduced PD risk and slower progression, though optimal thresholds remain incompletely defined. Aerobic exercise improves cardiovascular fitness and may aid clearance of pathogenic proteins; resistance training counters sarcopenia and bradykinesia; balance training reduces falls; and mind-body exercises (e.g., Tai Chi) integrate motor and cognitive components. Multimodal regimens are often most beneficial. High-intensity aerobic exercise appears particularly effective in early PD, enhancing neural connectivity and mitigating disease progression in randomized trials. Most evidence supports supervised sessions occurring 3-5 times per week, lasting 30-60 min, adapted to individual tolerance and disease stage. In conclusion, this narrative review outlines a comprehensive precision medicine framework for exercise intervention in PD, moving beyond symptomatic management towards targeting underlying pathophysiology. By stratifying patients based on genetic, phenotypic, and staging characteristics, and by leveraging digital technology for dynamic personalization, exercise therapy can be transformed into a more potent, individualized, and disease-modifying strategy. Future research must validate these biomarker-driven approaches in large-scale trials and establish definitive guidelines for translating precision exercise into clinical practice.

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周子贵,颜敏,温潇,王慧,刘国强,田雪文.帕金森病精准运动干预的多维体系:基于遗传分型、运动亚型、临床分期和可穿戴数字生物标志物的动态调控[J].生物化学与生物物理进展,2025,52(11):2788-2801

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  • 收稿日期:2025-06-03
  • 最后修改日期:2025-11-11
  • 录用日期:2025-09-26
  • 在线发布日期: 2025-09-28
  • 出版日期: 2025-11-28
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