Zhu Yongqiang, Xi Qi, Liu Yan, Zhou Yang, Liao Jun, Wu Qiong
Shengjing Hospital of China Medical University, Liaoning, 110004, China.
The first Hospital of China Medical University, Liaoning, 110001, China.
Biomaterials. 2026 Feb;325:123548. doi: 10.1016/j.biomaterials.2025.123548. Epub 2025 Jul 10.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects dopaminergic neurons in the substantia nigra. Its multifactorial pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, α-synuclein aggregation, neuroinflammation, and alterations in the gut microbiome, ultimately leading to neuronal deficits and debilitating motor and nonmotor symptoms. Although conventional therapies provide temporary relief, their efficacy tends to wane over time or produce adverse effects. Exosome-based therapeutic strategies are a promising alternative, and we highlight the unique advantages of exosomes, including their biocompatibility, low immunogenicity, and ability to cross the blood-brain barrier, thereby facilitating the targeted delivery of neuroprotective and anti-inflammatory medications to affected regions. We also discuss recent advances in exosome engineering to improve cargo loading, enhance cell specificity and improve efficacy. However, large-scale exosome production, targeted delivery and long-term safety remain major challenges. Early-phase clinical trials of exosome-based therapies in other neurodegenerative conditions have demonstrated acceptable tolerability, and ongoing preclinical studies in PD models suggest potential efficacy, laying the groundwork for future clinical translation.
帕金森病（PD）是一种进行性神经退行性疾病，主要影响黑质中的多巴胺能神经元。其多因素致病机制包括氧化应激、线粒体功能障碍、α-突触核蛋白聚集、神经炎症以及肠道微生物群的改变，最终导致神经元缺陷以及使人衰弱的运动和非运动症状。尽管传统疗法能提供暂时缓解，但随着时间推移其疗效往往会减弱或产生不良反应。基于外泌体的治疗策略是一种有前景的替代方法，我们强调了外泌体的独特优势，包括它们的生物相容性、低免疫原性以及穿越血脑屏障的能力，从而促进神经保护和抗炎药物向受影响区域的靶向递送。我们还讨论了外泌体工程在改善货物装载、增强细胞特异性和提高疗效方面的最新进展。然而，大规模外泌体生产、靶向递送和长期安全性仍然是主要挑战。基于外泌体疗法在其他神经退行性疾病中的早期临床试验已证明具有可接受的耐受性，并且目前在帕金森病模型中的临床前研究表明有潜在疗效，为未来的临床转化奠定了基础。
