Introduction: PD is a progressive neurodegenerative disorder, which is associated with the deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor symptoms. Pathogenesis includes alpha-synuclein aggregation and Lewy bodies, neuroinflammation, and oxidative stress. The breakdown of the blood-brain barrier (BBB) via tight junctions and disturbed transporter activity has been identified as a factor in the evolution of PD. Methods: The review is a synthesis of evidence provided by preclinical and clinical studies that examine the connection between BBB dysfunction and the pathogenesis of PD. PubMed, Web of Science, and Google Scholar were used to source the literature, and studies that show BBB permeability, α-synuclein pathology, and therapeutic interventions of BBB integrity were used as a limiting factor. Results: Evidence indicates that the activation of BBB damage by disruptive activity allows the intrusion of neurotoxic factors and inflammatory agents in the central nervous system to worsen the degeneration of dopaminergic neurons. The changes in endothelial tight junction proteins, transporters, and immune cell infiltrations have remained consistent in PD models. Preclinical treatments, including neuroprotective therapeutics, anti-inflammatory medications, and treatments that alter the BBB permeability to be used in delivering drugs to specific brain locations, have demonstrated positive outcomes in the survival of neurons and motor activity. Discussion: BBB dysfunction in PD appears to be an outcome and a cause of neurodegeneration, which forms a vicious cycle with neuroinflammation and α-synuclein deposition. Modifying permeability by targeting BBB repair pathways and selecting particular mechanisms to enhance permeability are promising disease-modifying therapies. Conclusion: BBB integrity is a very important but under-investigated element of PD pathogenesis. Understanding its interplay with neuroinflammation and protein aggregation may yield novel therapeutic targets and improve drug delivery approaches in PD management.
Singh et al. (2026) studied this question.