Neurodegenerative disorders constitute a heterogeneous group of chronic, progressive conditions characterized by the selective and irreversible degeneration of neurons in the central and peripheral nervous systems. Prominent among these are Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), each marked by distinct pathological hallmarks yet sharing common underlying mechanisms, including protein misfolding, mitochondrial dysfunction, and, most critically, oxidative stress. Oxidative stress arises from a persistent imbalance between the generation of reactive oxygen species (ROS) and the cellular antioxidant defense mechanisms, leading to a disruption in redox homeostasis. The resultant accumulation of ROS aggravates neuronal damage through lipid peroxidation, protein oxidation, and DNA fragmentation, further perpetuating neuroinflammation and apoptotic signaling cascades. The failure of endogenous redox-regulatory systems underscores the urgent need for therapeutic interventions capable of restoring oxidative balance while minimizing off-target effects. In this context, photo-drugs, a novel class of photo-responsive compounds, emerge as a compelling therapeutic strategy, lifting the principles of photo-biomodulation (PBM) to modulate cellular redox states with high spatiotemporal precision. PBM operates through the targeted delivery of low-energy light at specific wavelengths (typically within the red to near-infrared spectrum, 600–1000 nm), which interacts with mitochondrial chromophores, particularly cytochrome c oxidase, to enhance electron transport chain efficiency, attenuate ROS production, and promote ATP synthesis. Unlike conventional pharmacological agents, which often exhibit systemic toxicity and limited blood-brain barrier permeability, photo-drugs offer a non-invasive, multi-targeted approach capable of precise neuromodulation with minimal adverse effects. This chapter sheds light on the mechanistic basis by which photo-drugs can rectify redox dysregulation in neurodegenerative pathologies, highlighting their potential as a next-generation therapeutic paradigm. By integrating advances in photochemistry, molecular biology, and neuropharmacology, we start exploring the translational prospects of photo-drugs in mitigating neuronal degeneration, thereby paving the way for safer, more efficacious treatments in clinical neurology. Through a critical examination of preclinical and emerging clinical evidence, we aim to delineate how photo-biomodulation-based interventions could redefine therapeutic strategies, ultimately contributing to the advancement of human health in the face of neurodegenerative decline.

Photodrugs: Role of Redox Regulation in Neurodegenerative Diseases

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发表日期：

2026年

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Yashi Mahendra,
Hagera Dilnashin

摘要

Neurodegenerative disorders constitute a heterogeneous group of chronic, progressive conditions characterized by the selective and irreversible degeneration of neurons in the central and peripheral nervous systems. Prominent among these are Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), each marked by distinct pathological hallmarks yet sharing common underlying mechanisms, including protein misfolding, mitochondrial dysfunction, and, most critically, oxidative stress. Oxidative stress arises from a persistent imbalance between the generation of reactive oxygen species (ROS) and the cellular antioxidant defense mechanisms, leading to a disruption in redox homeostasis. The resultant accumulation of ROS aggravates neuronal damage through lipid peroxidation, protein oxidation, and DNA fragmentation, further perpetuating neuroinflammation and apoptotic signaling cascades. The failure of endogenous redox-regulatory systems underscores the urgent need for therapeutic interventions capable of restoring oxidative balance while minimizing off-target effects. In this context, photo-drugs, a novel class of photo-responsive compounds, emerge as a compelling therapeutic strategy, lifting the principles of photo-biomodulation (PBM) to modulate cellular redox states with high spatiotemporal precision. PBM operates through the targeted delivery of low-energy light at specific wavelengths (typically within the red to near-infrared spectrum, 600–1000 nm), which interacts with mitochondrial chromophores, particularly cytochrome c oxidase, to enhance electron transport chain efficiency, attenuate ROS production, and promote ATP synthesis. Unlike conventional pharmacological agents, which often exhibit systemic toxicity and limited blood-brain barrier permeability, photo-drugs offer a non-invasive, multi-targeted approach capable of precise neuromodulation with minimal adverse effects. This chapter sheds light on the mechanistic basis by which photo-drugs can rectify redox dysregulation in neurodegenerative pathologies, highlighting their potential as a next-generation therapeutic paradigm. By integrating advances in photochemistry, molecular biology, and neuropharmacology, we start exploring the translational prospects of photo-drugs in mitigating neuronal degeneration, thereby paving the way for safer, more efficacious treatments in clinical neurology. Through a critical examination of preclinical and emerging clinical evidence, we aim to delineate how photo-biomodulation-based interventions could redefine therapeutic strategies, ultimately contributing to the advancement of human health in the face of neurodegenerative decline.