From Neurotoxicity to Neuroprotection: Photobiomodulation against the Effects of the SARS-CoV-2 Spike Protein in an Alzheimer's Disease Model

Alzheimer's Disease (AD) is the leading cause of dementia and represents one of the greatest global health challenges, affecting not only patients but also their families. Still without a cure, current treatments only alleviate symptoms. The COVID-19 (Coronavirus Disease 2019) pandemic highlighted neurological complications associated with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), particularly the Spike protein. This study aimed to investigate the potential neurotoxic effects of recombinant Spike protein using two-dimensional (2D) in vitro neuronal models established for AD, as well as the therapeutic potential of photobiomodulation (PBM) with red LED (Light Emitting Diode) (660 nm) in attenuating these effects. Differentiated SH-SY5Y (human neuroblastoma) cells were exposed to Spike protein (0.5 µg/mL) and oxidative stress by H₂O₂ (Hydrogen peroxide) 200 µM, individually or combined, with and without PBM (3 J/cm²). Cell viability was assessed using the Alamar Blue assay, and immunofluorescence characterized nuclear (Hoechst), mitochondrial (Mitotracker), actin (phalloidin), and focal adhesion (FAK) alterations. Immunofluorescence revealed mitochondrial fragmentation, actin disorganization, FAK redistribution, and nuclear condensation. The results demonstrated that Spike protein induced neurotoxicity in AD models, notably aggravated by oxidative stress. In contrast, PBM represented a promising intervention strategy, exerting a neuroprotective effect that preserves viability, mitochondrial integrity, nuclear morphology, and cytoskeletal organization. PBM thus appears to modulate mitochondrial function and mitigate oxidative stress, offering a potential therapeutic pathway to attenuate neuronal damage induced by Spike protein.