Photobiomodulation in Parkinson's disease: From pathogenesis to intervention

Parkinson's disease (PD) is a progressive neurodegenerative disorder clinically characterized by bradykinesia, rest tremor, rigidity, and postural instability. Its core pathological features include the progressive loss of dopaminergic neurons within the substantia nigra pars compacta, striatal dopamine depletion, and intracellular accumulation of misfolded α-Synuclein (α-Syn)-rich Lewy inclusions that trigger neuronal dysfunction and cell death. Despite substantial research efforts, existing pharmacological strategies targeting α-Syn and dopaminergic neurons show limited capacity to halt or reverse PD progression, creating an urgent need for novel alternative therapeutic interventions. Photobiomodulation (PBM) is a non-invasive phototherapy that delivers photonic energy to biological tissues using visible and near-infrared light. Preclinical studies have documented neuroprotective signals linked to PBM in experimental PD models; however, clinical studies to date provide only preliminary and inconsistent evidence regarding safety and possible symptomatic benefit. This narrative review outlines the mechanistic rationale, preclinical findings, clinical observations, and key translational limitations for PBM as an investigational adjunctive intervention in PD. We first elaborate on PD-related pathological mechanisms, followed by an in-depth discussion of PBM-mediated biological actions, and consolidate recent evidence for its anti-PD applications in preclinical settings. Available preclinical data suggest PBM could modulate mitochondrial function, neuroinflammation, dopaminergic-neuron survival, and responses along the microbiota-gut-brain axis in experimental PD models, though direct evidence supporting modification of α-synuclein aggregation or propagation remains sparse. Clinical observations support procedural feasibility and acceptable short-term safety profiles. Nevertheless, definitive clinical efficacy cannot be confirmed given small sample sizes, heterogeneous intervention protocols, and inconsistent outcomes from controlled trials. PBM should currently be regarded as an investigational adjunctive strategy rather than an established therapy for PD.