A β‐Glucosyl Sterol Probe for in situ Fluorescent Labelling in Neuronal Cells to Investigate Neurodegenerative Diseases

• Published in: Chemistry : a European journal Vol. 30; no. 41; pp. e202400778 - n/a
• Main Authors: Borsato, Giuseppe, Carnio, Francesco, Lunardon, Sara, Moletta, Mattia, Pavan, Giulio, Terrin, Francesca, Scarso, Alessandro, Plotegher, Nicoletta, Fabris, Fabrizio
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 19.07.2024; Wiley Subscription Services, Inc
• Subjects: Alkynes; Animals; Chemistry; Chemistry, Multidisciplinary; Fluorescence; fluorescent biomarker; Fluorescent Dyes - chemistry; glucosyl-sterols; Humans; Labeling; Localization; lysosome; Lysosomes; Lysosomes - chemistry; Lysosomes - metabolism; neurodegenerative disease; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neurons - metabolism; Parkinson's disease; Physical Sciences; Science & Technology; Sterols - chemistry; DOMAIN; neurodegenerative disease; Parkinson's disease; CHOLESTEROL GLUCOSYLATION; fluorescent biomarker; GLYCOSYLATION; GUAM; PROTEINS; lysosome; GLUCOCEREBROSIDASE MUTATIONS; glucosyl-sterols
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202400778

A β‐glucosyl sterol probe bearing a terminal alkyne moiety for fluorescent tagging enables the investigation of the neuronal and intracellular localization of this class of compounds involved in neurodegenerative diseases. The compound showed localization in the neuronal cells, with marked differences in the uptake and metabolism leading to enhanced persistence with respect to the un‐glycosylated sterol analogue. In addition, a different impact was observed towards lysosomes, with the simple sterol probe showing the enlargement of the lysosome structures, while the β‐glucosyl sterol was less capable to alter the morphology of this specific organelle. Aiming at tackling neurodegenerative diseases, the potential effect of β‐glucosyl sterol on neuronal cells is investigated by means of fluorescent labelling of a synthetic derivative. Marked differences in neuron accumulation, metabolism, and impact on the lysosomes with respect to the un‐glycosylated cholesterol derivative were observed.