Parkinson's disease (PD) is a brain disorder in which neuronal cells responsible for the release of dopamine, a neurotransmitter that controls movement, are degenerated or impaired in the substantia nigra and basal ganglia. The disease typically affects people over the age of 5 and presents with a variety of motor and nonmotor dysfunctions, which are unique to each person. The impairment of the blood-brain barrier (BBB) and blood retinal barrier (BRB) due to age-related causes such as weakness of tight junctions or rare genetic factors allows several metabolic intermediates to reach and accumulate inside neurons such as Lewy bodies and α-synuclein, disrupting neuronal homeostasis and leading to genetic and epigenetic changes, e.g., damage to the DNA repair system. This perspective highlights the importance of blood barriers, such as the BBB and BRB, in the progression of PD, as the aggregation of Lewy bodies and α-synuclein disrupts neuronal homeostasis. Genetic and epigenetic factors, neuroinflammation, oxidative stress, and mitochondrial dysfunction play crucial roles in the progression of the disease. The implications of these findings are significant; identifying synaptic dysfunction could lead to earlier diagnosis and treatment, while developing targeted therapies focused on preserving synaptic function may slow or halt disease progression. Understanding the various genetic forms of PD could enable more personalized medicine approaches, and using patient-derived midbrain neurons for research may improve the accuracy of PD models due to the implications of an impaired BBB.
© 2024 The Authors. Published by American Chemical Society.