Acupuncture and mitochondrial homeostasis in central nervous system diseases: A multi-target perspective

Mitochondrial dysfunction has been considered as a central pathological contributor to neuronal injury, impaired energy metabolism, and limited functional recovery in central nervous system (CNS) diseases. Acupuncture has been widely employed in the prevention, treatment, and rehabilitation of CNS diseases. However, its regulatory effects on mitochondrial homeostasis have not yet been systematically reviewed. A comprehensive search of major English and Chinese databases was performed. Using a narrative review approach, relevant studies examining the effects of acupuncture on mitochondrial homeostasis in CNS diseases were analyzed to summarize key outcomes, underlying mechanisms, and current limitations. Acupuncture may modulate mitochondrial homeostasis in CNS diseases through multiple mechanisms, including increased mitochondrial abundance, preservation of mitochondrial ultrastructure, enhanced oxidative phosphorylation, elevated adenosine triphosphate production, reduced oxidative stress, and regulation of mitochondrial quality control (MQC) processes. Mechanistic studies implicate pathways such as Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator-1α/NRF1/mitochondrial transcription factor A pathway, PTEN-induced kinase 1/Parkin-related signaling, and Nrf2/Keap1- mediated redox regulation. Acupuncture appears to confer neuroprotection and promote neural repair through the coordinated regulation of these targets and processes. However, significant limitations persist, including insufficient assessment of dynamic mitochondrial function and flux, limited cell type-specific and time-resolved validation, insufficient evidence from genetic or pharmacological intervention studies, and substantial heterogeneity in stimulation parameters and outcome measures. These issues restrict cross-study comparisons and clinical translation. Future research should focus on rigorous validation of the mechanisms by which acupuncture regulates mitochondrial homeostasis, emphasizing dynamic functional assessments, cell type-specific analyses, and causal mechanistic investigations. Integrating mechanistic markers with functional outcomes and clinically relevant biomarkers may facilitate translational applications. Overall, the modulation of mitochondrial homeostasis represents a promising pathway through which acupuncture exerts neuroprotective and restorative effects in CNS diseases. 背景: 线粒体功能障碍被认为是中枢神经系统疾病中神经元损伤,能量代谢紊乱及功能恢复受限的重要病理基础.针灸已被广泛应用于中枢神经系统疾病的防治与康复, 但对线粒体稳态的调控机制尚缺乏系统总结. 方法: 本文对主要中英文数据库进行了结构化检索, 采用叙述性综述方法, 对针灸调控中枢神经系统疾病线粒体稳态的相关研究进行归纳分析, 以总结其主要作用环节,潜在机制及现存问题. 结果: 目前研究表明, 针灸可从多个层面调节中枢神经系统疾病中的线粒体稳态, 主要为增加线粒体数量,改善线粒体超微结构,增强氧化磷酸化功能,促进三磷酸腺苷合成,减轻氧化应激损伤以及调控线粒体质量控制相关过程.现有机制研究多涉及SIRT1/ PGC-1α/NRF1/TFAM通路,PINK1/Parkin相关通路, 以及Nrf2/Keap1介导的氧化还原调控通路. 发现: 目前研究提示其可能通过多靶点,多环节协同作用参与神经保护与神经修复, 但存在线粒体功能动态变化及通量评估不足,细胞类型特异性和时间序列验证不充分,缺乏遗传学或药理学干预支持的验证性证据, 以及不同研究间刺激参数和观察指标差异较大等问题, 这些限制了研究结果的比较及其临床转化. 启示: 未来应加强针灸调控线粒体稳态关键机制的系统验证, 重视动态功能评价,细胞类型分辨及因果机制研究, 并推动机制指标与功能结局及可转化生物标志物之间的关联分析.线粒体稳态是针灸在中枢神经系统疾病中发挥神经保护与神经修复作用的重要共同通路之一.