Aim

Our study investigates the link between neuroinflammation in the olfactory bulb (OB) and Parkinson’s Disease (PD). We aim to understand how environmental factors, such as viruses and particles, trigger a cascade of events leading to ?-synuclein aggregation and the development of PD.

Methods

We conducted histological studies of PD brains, pinpointing ?-synuclein abnormalities in the anterior olfactory structures at Braak's stage 1. Our study expanded post-mortem examinations to include the OB. We assessed:

• The vulnerability of the olfactory epithelium and OB to inflammation, considering age-related epithelial changes.
• The role of microglia in the OB and their potential as a barrier against exogenous pathogens.
• The entry of toxins, viruses, and nanoparticles into the OB, using animal models.

Results

Our research highlights the association between viral infections and PD, including the 1918 influenza pandemic and childhood infections. Chronic rhinitis and the presence of influenza A virus in PD brains further support this link.

• Animal studies reveal the impact of neurotropic viruses entering via the olfactory route, leading to ?-synuclein aggregation and widespread inflammation.
• Activated microglia play a pivotal role in pathogen clearance but also disrupt the blood-brain barrier (BBB), particularly in the OB.
• Metal particles such as aluminum and iron were identified as potential contributors to PD through chronic inflammation.

Conclusion

This study unveils the critical role of OB neuroinflammation as a trigger for PD. Environmental factors significantly influence PD pathogenesis, offering potential avenues for intervention and prevention. Our findings enhance the understanding of this neurodegenerative disease and open new prospects for future PD research and treatments.