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

Abstract

Background

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.

Methods

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.

Results

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.

Findings

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.

Conclusion

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.