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 (MoS2) and molybdenum diselenide (MoSe2) nanoflowers (NFs) in neurons and astrocytes exposed to α-syn aggregates.

It was found that MoS2 and MoSe2 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 MoS2 or MoSe2 NFs could be used as novel therapeutic to decelerate the progression of PD. The authors would like to acknowledge the Material Characterization Facility at Texas A&M University [RRID: SCR_022202] and the Texas A&M University Laboratory for Synthetic-Biologic Interactions [RRID: SCR_022287] for experimental help.

The authors thank the Texas A&M University academic institutional license [CC BY 4.0] for providing access to BioRender. Figures 2, 4, and 5 were partially generated with BioRender.com (https://BioRender.com/xrc9n2q, https://BioRender.com/yy6862e, and https://BioRender.com/ii4cy0j, respectively). We are grateful to the National Institute of Health for the financial support provided (R35GM142869).

Interdisciplinary Program in Genetics and Genomics, Texas A&M University, College Station, TX, USA Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA Charles L. Mitchell, Mikhail Matveyenka, Harris C. Brown, Jessica Aldape, Payton Moore, Kha-Tran Nguyen, John C.

Walker, Bryce Pearson, Joshua Skrehot, Daniel Warren & Dmitry Kurouski The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.