Artificial light-mediated sleep disruption during night in urbanised establishments has emerged as a man-made hazard for its silent contribution in the development of numerous health issues, including neurodegenerative disorders (Shen et al., 2023; Voigt et al., 2024; Filippini et al., 2024). Several studies have long associated the detrimental effects of undesirable exposure to light, especially the blue component of the visible spectrum, with physical fitness and longevity (Sheeba et al., 2000; McLay et al., 2017; Nash et al., 2019). In line, aggravated neurodegeneration, impaired locomotion, and shortening of life span have been frequently observed in response to aberrant light treatment (De Magalhaes Filho et al., 2018; Song et al., 2022). However, despite the accumulating evidence, the impact of unnatural light exposure on the pathophysiology of neurodegenerative disorders is largely unknown.

Tauopathies, including disorders such as Frontotemporal Dementia, Pick's Disease, and Alzheimer's Disease, are a group of age-onset progressive neurodegenerative disorders characterized by the accumulation of pathogenically hyperphosphorylated microtubule-associated tau protein. These pathological tau species form toxic aggregates and neurofibrillary tangles (NFTs) within neurons, contributing to synaptic dysfunction, neuronal loss, and cognitive decline (Olfati et al., 2022). This pathogenic hyperphosphorylation of tau and its progressive deposition as NFTs in the brain is a key trigger that drives disease onset as well as its progression (Liu et al., 2020). In addition, impaired clearance mechanisms specifically, mitophagy, autophagy, and the brain's glymphatic system also contribute to the accumulation of pathogenic tau and increased disease severity (Fang et al., 2019; Harrison et al., 2020). It has been observed that aberrant expression of pathogenic human tau disrupts the normal sleep/wake cycle and circadian rhythm in Drosophila and mouse models (Kim et al., 2018; Stevanovic et al., 2017; Zhu et al., 2018; Buhl et al., 2019; Cassar et al., 2020). Interestingly, an enforced impairment of the sleep/wake cycle and circadian rhythm has emerged as a contributory factor that aggravates the disease severity (Stevanovic et al., 2017; Creekmore et al., 2024; Son et al., 2024). Consistently, impaired autophagic flux and dysfunction of the glymphatic system under sleep-deprived conditions have been increasingly linked to accelerated neurodegeneration (Nedergaard and Goldman, 2020; Voumvourakis et al., 2023). In agreement, dim light-mediated added decay in the sleep/wake cycle in Drosophila tauopathy model strengthens the notion that irregular exposure to light exaggerates tau-driven neurodegeneration (Kim et al., 2018). However, the potential impact of the uninterrupted exposure to light on the key disease parameters and pathogenic event(s) such as tau hyperphosphorylation and formation of neurotoxic tau aggregates/NFTs is lacking. Such intricacies serve as a conduit for identifying the kinases/phosphatases and associated molecular mechanisms involved in light-mediated alterations to disease pathogenesis, and may lay the foundation for designing suitable therapeutic interventions in the future.

Thus, the present study utilizes Drosophila models of human tauopathies to investigate the effect(s) of prolonged exposure to continuous light on the age-dependent progression of the disease severity. Our study, for the first time, demonstrates that continuous exposure to white light magnifies the intensity of disease severity early in time and in an accelerated time frame, plausibly due to impaired sleep/wake cycle.