Transition Metal Dichalcogenide Nanoflowers Rescue Immune Cells from the Cytotoxic Effects of Amyloid Aggregates.

Parkinson's disease (PD) is a severe pathology caused by a progressive degeneration of neurons in the substantia nigra pars compacta, hypothalamus, and thalamus. Although etiology of PD remains unclear, accumulating evidence indicates that neurodegenerative effects are triggered by the abrupt aggregation of α-synuclein (α-Syn), a small membrane protein that is responsible for cell vesicle trafficking. α-Syn aggregates are highly toxic to neurons and immune cells present in the brain, including macrophages, microglia, and dendritic cells. Transition metal dichalcogenide nanoflowers (TMD NFs) are novel nanomaterials with unique optical and biological properties. However, their effects on the immune system remain poorly understood. In this study, we investigate cytoprotective properties of molybdenum disulfide (MoS2) and molybdenum diselenide (MoSe2) NFs on macrophages, microglia, and dendritic cells exposed to α-Syn fibrils. We found that MoSe2 NFs exerted strong cytoprotective properties fully mitigating toxic effects of α-Syn fibrils, while MoS2 NFs were found to be significantly less potent in rescuing immune cells from α-Syn aggregates. At the same time, MoS2 NFs triggered polarization of macrophages into M1 and dendritic cells into M2 phenotypes, while an increase in both M1 and M2 was observed in microglia exposed to MoS2 NFs. MoSe2 NFs did not trigger polarization of DC cells and microglia in M1/M2 phenotypes, while MoSe2 NFs-facilitated polarization of macrophages into M1 was observed. These results indicate that TMD NFs could be used to improve viability of immune cells and attenuate their phenotypes, which, ultimately, can be used to treat PD and other neurodegenerative pathologies.