New cellular imaging-based method to distinguish the SPG4 subtype of hereditary spastic paraplegia.
SPG4
biomarker
hereditary spastic paraplegia
microtubule
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
07
02
2023
received:
23
12
2022
accepted:
16
02
2023
medline:
8
5
2023
pubmed:
24
2
2023
entrez:
23
2
2023
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
Spastin
EC 3.6.4.3
SPAST protein, human
EC 5.6.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1734-1744Informations de copyright
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
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