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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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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    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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ZHOU Zi-Gui, YAN Min, WEN Xiao, WANG Hui, LIU Guo-Qiang, TIAN Xue-Wen. Multidimensional System of Precision Exercise Interventions for Parkinson’s Disease: Dynamic Regulation Based on Genetic Typing, Motor Subtypes, Clinical Staging, and Wearable Digital Biomarkers[J]. Progress in Biochemistry and Biophysics,2025,52(11):2788-2801

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History
  • Received:June 03,2025
  • Revised:November 11,2025
  • Adopted:September 26,2025
  • Online: September 28,2025
  • Published: November 28,2025
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