Foo Aaron Song Chuan, Soong Tuck Wah, Yeo Tseng Tsai, Lim Kah-Leong
Department of Physiology, National University of Singapore, Singapore, Singapore.
Division of Neurosurgery, Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore.
Front Aging Neurosci. 2020 Apr 3;12:89. doi: 10.3389/fnagi.2020.00089. eCollection 2020.
As the main driver of energy production in eukaryotes, mitochondria are invariably implicated in disorders of cellular bioenergetics. Given that dopaminergic neurons affected in Parkinson's disease (PD) are particularly susceptible to energy fluctuations by their high basal energy demand, it is not surprising to note that mitochondrial dysfunction has emerged as a compelling candidate underlying PD. A recent approach towards forestalling dopaminergic neurodegeneration in PD involves near-infrared (NIR) photobiomodulation (PBM), which is thought to enhance mitochondrial function of stimulated cells through augmenting the activity of cytochrome C oxidase. Notwithstanding this, our understanding of the neuroprotective mechanism of PBM remains far from complete. For example, studies focusing on the effects of PBM on gene transcription are limited, and the mechanism through which PBM exerts its effects on distant sites (i.e., its "abscopal effect") remains unclear. Also, the clinical application of NIR in PD proves to be challenging. Efficacious delivery of NIR light to the substantia nigra pars compacta (SNpc), the primary site of disease pathology in PD, is fraught with technical challenges. Concerted efforts focused on understanding the biological effects of PBM and improving the efficiency of intracranial NIR delivery are therefore essential for its successful clinical translation. Nonetheless, PBM represents a potential novel therapy for PD. In this review, we provide an update on the role of mitochondrial dysfunction in PD and how PBM may help mitigate the neurodegenerative process. We also discussed clinical translation aspects of this treatment modality using intracranially implanted NIR delivery devices.
作为真核生物能量产生的主要驱动者，线粒体总是与细胞生物能量学紊乱有关。鉴于帕金森病（PD）中受影响的多巴胺能神经元因其高基础能量需求而特别容易受到能量波动的影响，线粒体功能障碍已成为PD潜在的重要病因也就不足为奇了。最近一种预防PD中多巴胺能神经退行性变的方法涉及近红外（NIR）光生物调节（PBM），人们认为它通过增强细胞色素C氧化酶的活性来增强受刺激细胞的线粒体功能。尽管如此，我们对PBM神经保护机制的理解仍远未完善。例如，专注于PBM对基因转录影响的研究有限，PBM对远处部位发挥作用的机制（即其“远隔效应”）仍不清楚。此外，NIR在PD中的临床应用也颇具挑战性。将NIR光有效传递到黑质致密部（SNpc）（PD疾病病理的主要部位）充满了技术挑战。因此，集中精力理解PBM的生物学效应并提高颅内NIR传递效率对于其成功的临床转化至关重要。尽管如此，PBM仍是一种潜在的PD新疗法。在这篇综述中，我们更新了线粒体功能障碍在PD中的作用以及PBM如何有助于减轻神经退行性变过程。我们还讨论了使用颅内植入式NIR传递装置的这种治疗方式的临床转化方面。
