Background and purpose: Microtubule defects are a common feature in several neurodegenerative disorders, including hereditary spastic paraplegia. The most frequent form of hereditary spastic paraplegia is caused by mutations in the SPG4/SPAST gene, encoding the microtubule severing enzyme spastin. To date, there is no effective therapy available but spastin-enhancing therapeutic approaches are emerging; thus prognostic and predictive biomarkers are urgently required. Methods: An automated, simple, fast and non-invasive cell imaging-based method was developed to quantify microtubule cytoskeleton organization changes in lymphoblastoid cells and peripheral blood mononuclear cells. Results: It was observed that lymphoblastoid cells and peripheral blood mononuclear cells from individuals affected by SPG4-hereditary spastic paraplegia show a polarized microtubule cytoskeleton organization. In a pilot study on freshly isolated peripheral blood mononuclear cells, our method discriminates SPG4-hereditary spastic paraplegia from healthy donors and other hereditary spastic paraplegia subtypes. In addition, it is shown that our method can detect the effects of spastin protein level changes. Conclusions: These findings open the possibility of a rapid, non-invasive, inexpensive test useful to recognize SPG4-hereditary spastic paraplegia subtype and evaluate the effects of spastin-enhancing drug in non-neuronal cells.

New cellular imaging-based method to distinguish the SPG4 subtype of hereditary spastic paraplegia / Sardina, Francesca; Valente, Davide; Fattorini, Gaia; Cioffi, Ettore; Zanna, Gianmarco Dalla; Tessa, Alessandra; Trisciuoglio, Daniela; Soddu, Silvia; Santorelli, Filippo M; Casali, Carlo; Rinaldo, Cinzia. - In: EUROPEAN JOURNAL OF NEUROLOGY. - ISSN 1468-1331. - 30:6(2023), pp. 1734-1744. [10.1111/ene.15756]

New cellular imaging-based method to distinguish the SPG4 subtype of hereditary spastic paraplegia

Sardina, Francesca
;
Fattorini, Gaia;Cioffi, Ettore;Zanna, Gianmarco Dalla;Trisciuoglio, Daniela;Santorelli, Filippo M;
2023

Abstract

Background and purpose: Microtubule defects are a common feature in several neurodegenerative disorders, including hereditary spastic paraplegia. The most frequent form of hereditary spastic paraplegia is caused by mutations in the SPG4/SPAST gene, encoding the microtubule severing enzyme spastin. To date, there is no effective therapy available but spastin-enhancing therapeutic approaches are emerging; thus prognostic and predictive biomarkers are urgently required. Methods: An automated, simple, fast and non-invasive cell imaging-based method was developed to quantify microtubule cytoskeleton organization changes in lymphoblastoid cells and peripheral blood mononuclear cells. Results: It was observed that lymphoblastoid cells and peripheral blood mononuclear cells from individuals affected by SPG4-hereditary spastic paraplegia show a polarized microtubule cytoskeleton organization. In a pilot study on freshly isolated peripheral blood mononuclear cells, our method discriminates SPG4-hereditary spastic paraplegia from healthy donors and other hereditary spastic paraplegia subtypes. In addition, it is shown that our method can detect the effects of spastin protein level changes. Conclusions: These findings open the possibility of a rapid, non-invasive, inexpensive test useful to recognize SPG4-hereditary spastic paraplegia subtype and evaluate the effects of spastin-enhancing drug in non-neuronal cells.
2023
SPG4; biomarker; hereditary spastic paraplegia; microtubule
01 Pubblicazione su rivista::01a Articolo in rivista
New cellular imaging-based method to distinguish the SPG4 subtype of hereditary spastic paraplegia / Sardina, Francesca; Valente, Davide; Fattorini, Gaia; Cioffi, Ettore; Zanna, Gianmarco Dalla; Tessa, Alessandra; Trisciuoglio, Daniela; Soddu, Silvia; Santorelli, Filippo M; Casali, Carlo; Rinaldo, Cinzia. - In: EUROPEAN JOURNAL OF NEUROLOGY. - ISSN 1468-1331. - 30:6(2023), pp. 1734-1744. [10.1111/ene.15756]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1693057
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