Exosome mimetic nanoparticles for siRNA based targeting of α-synuclein and neuroinflammation in Parkinson's disease.

BACKGROUND

Parkinson's disease (PD) is a neurodegenerative disorder caused by degeneration of dopaminergic neurons and accumulation of α-synuclein protein, leading to sustained neuroinflammation.

OBJECTIVE

This review analyze the application of gene silencing mediated by small interfering RNAs for α-synuclein protein and inflammatory factors in the treatment of PD. The use of exosomes-mimetic nanoparticles (EM-NPs) for siRNA delivery will be highlighted in particular.

METHODS

This review highlights recent findings on the molecular mechanisms involved in PD, the development of siRNA drugs, and the potential of EM-NP-mediated siRNA delivery systems for CNS delivery.

RESULTS

siRNA provides an excellent approach to silence specific disease-related genes, such as SNCA and inflammatory factors. Nevertheless, its practical application is hampered by low stability, enzymatic degradation, difficulty crossing the BBB, and non-specific activity. EM-NPs combine the advantages of biocompatibility and scalability that natural exosomes possess and synthetic nanoparticles exhibit, respectively.

CONCLUSION

The delivery of siRNA molecules via EM-NPs could be considered an innovative disease-modifying approach toward treating PD patients, involving both pathological α-synuclein protein and neuroinflammation.