Parkinson’s disease is the second most common chronic neurodegenerative disorder. Pathogenesis involves the loss of dopaminergic neurons in the substantia nigra due to the accumulation of α-synuclein aggregates. In traumatic brain injury (TBI)-induced Parkinson’s disease, increased nitrosative and oxidative stress caused by elevated levels of reactive nitrogen species can promote post-translational modification and α-synuclein aggregation, disrupting normal brain functions. In this study, sodium nitrite (NaNO 2 ) was used as a nitrosative stress inducer to mimic the elevated reactive nitrogen species observed in TBI conditions, facilitating α-synuclein aggregation in vitro. Despite available therapies, including complex brain surgery, effective treatments remain limited. Naturally occurring polyphenols such as quercetin and myricetin have shown promise due to their antioxidant properties and synergistic effects with other treatments. Nitration-induced aggregation of α-synuclein was monitored using ThT fluorescence and turbidity as a function of time in the presence and absence of polyphenols. Results showed that quercetin and myricetin significantly inhibited fibril growth and promoted defibrillation. DLS, NTA, TEM, and AFM results demonstrate that shorter fibrils are formed in the presence of quercetin and myricetin, which are less toxic, as confirmed by the MTT assay. Most drugs fail to cross the blood-brain barrier, leading to reduced bioavailability. To overcome this, chitosan-poly(lactic-co-glycolic acid) (PLGA) nanoparticles were utilized as nanocarriers for polyphenol delivery due to their small size, biodegradability, low toxicity, biocompatibility, and controlled-release profile. The effects of polyphenol-loaded PLGA nanoparticles on α-synuclein aggregation were similar to those of polyphenol. These findings support the development of antioxidant-based therapies to mitigate Parkinson’s disease progression and improve understanding of TBI-induced neurodegeneration.
Prasad et al. (Sun,) studied this question.