Biology subjects

Kurouski, D.

Publications and source records attributed to Kurouski, D..

3 recordsLinked to original sources

bioRxiv2025

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

Parkinsons 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 -synuclein (-Syn), a small membrane protein that is responsible for cell vesicle trafficking. -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 -Syn fibrils. We found that MoSe2 NFs exerted strong cytoprotective properties fully mitigating toxic effects of -Syn fibrils, while MoS2 NFs were found to be significantly less potent in rescuing immune cells from -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.

neuroscience↗

bioRxiv2025

Neuroprotective Parkinson's Disease Therapeutic: Transition Metal Dichalcogenide Nanoflower Treatments Alleviate Pathological Cell Stress

Parkinsons disease (PD) is triggered by irreversible degeneration of dopaminergic neurons in the midbrain, hypothalamus, and thalamus. Although the underlying molecular etiology of these pathological processes remains unclear, progressive aggregation of alpha-synuclein (-syn) and mitochondrial dysfunction are two expected mechanisms implicated in neuronal degeneration. Accumulating evidence indicates that transition metal dichalcogenide (TMD) nanoflowers (NFs), a novel class of nanomaterials, can restore mitochondrial health by the activation of mitochondrial biogenesis. However, therapeutic potential of TMD NFs in PD remains unclear. The current study investigates the neuroprotective properties of molybdenum disulfide (MoS2) and molybdenum diselenide (MoSe2) nanoflowers (NFs) in neurons and astrocytes exposed to -syn aggregates. It was found that MoS2 and MoSe2 suppressed -syn-induced unfolded protein response (UPR) in the endoplasmic reticulum, and upregulated autophagy and exocytosis of -syn fibrils. TMD NFs also reversed -syn-induced damage of cell mitochondria, simultaneously stimulating mitochondrial biogenesis. As a result, a drastic decrease in ROS levels in both neurons and astrocytes was observed. These results show that MoS2 or MoSe2 NFs could fully rescue neurons and astrocytes from the cytotoxic effects of -syn fibrils. Neuroprotective properties of these novel nanomaterials were further explored in Caenorhabditis elegans that overexpress -syn. Nematodes that received NFs experienced a drastic reduction in the amount of aggregated -syn which resulted in a significant increase in C. elegans lifespan. These findings indicated that MoS2 or MoSe2 NFs could be used as novel therapeutic to decelerate the progression of PD.

neuroscience↗

bioRxiv2021

Phospholipids Uniquely Modify Secondary Structure of α-Synuclein Oligomers

Parkinson disease (PD) is a severe neurological disorder that affects more than a million people in the U.S. alone. A hallmark of PD is the formation of intracellular -synuclein (-Syn) protein aggregates called Lewy bodies (LBs). Although this protein does not have a particular localization in the central neural system, -Syn aggregates are primarily found in certain areas of midbrain, hypothalamus and thalamus. Microscopic analysis of LBs revealed fragments of lipid-rich membranes, organelles and vesicles. These and other pieces of experimental evidence suggest -Syn aggregation can be triggered by lipids. In this study, we used atomic force microscope Infrared (AFM-IR) spectroscopy to investigate structural organization of individual -Syn oligomers grown in the presence of two different phospholipids vesicles. AFM-IR is a modern optical nanoscopy technique that has single-molecule sensitivity and sub-diffraction spatial resolution. Our results show that -Syn oligomers grown in the presence of phosphatidylcholine have distinctly different structure than oligomers grown in the presence on phosphatidylserine. We infer that this occurs because of specific charges adopted by lipids, which in turn governs protein aggregation. We also found that protein to phospholipid ratio makes a substantial impact on the structure of -Syn oligomers. These findings demonstrate that -Syn is far more complex than expected from the perspective of structural organization of oligomeric species.

biophysics↗