Neuroprotective transition metal dichalcogenide nanoflower treatments alleviate pathological cell stress associated with Parkinson’s disease

Parkinson’s disease (PD) is triggered by irreversible degeneration of dopaminergic neurons in the midbrain, hypothalamus, and thalamus. Although the molecular etiology of pathology remains unclear, progressive aggregation of alpha-synuclein (α-syn) and mitochondrial dysfunction are two mechanisms implicated in neuronal degeneration. The current study investigates the neuroprotective properties of molybdenum disulfide (MoS 2 ) and molybdenum diselenide (MoSe 2 ) nanoflowers (NFs) in neurons and astrocytes exposed to α-syn aggregates. It was found that MoS 2 and MoSe 2 transcriptionally downregulated α-syn-induced unfolded protein response, and upregulated autophagy and exocytosis of α-syn fibrils. TMD NFs alleviated α-syn-induced damage of cell mitochondria, simultaneously altering metabolic adaptation, with a decrease in ROS levels observed. Neuroprotective properties were further explored in Caenorhabditis elegans that overexpress α-syn. Nematodes experienced a drastic reduction in the amount of aggregated α-syn which resulted in a significant increase in C. elegans lifespan. These findings indicate that MoS 2 or MoSe 2 NFs could be used as novel therapeutic to decelerate the progression of PD.