Pubblicazioni

Autori:

Marano, Massimo; Zizzo, Carmela; Malaguti, Maria Chiara; Bacchin, Ruggero; Cavallieri, Francesco; De Micco, Rosa; Spagnolo, Francesca; Bentivoglio, Anna Rita; Schirinzi, Tommaso; Bovenzi, Roberta; Ramat, Silvia; Erro, Roberto; Sorrentino, Cristiano; Sucapane, Patrizia; Pilotto, Andrea; Lupini, Alessandro; Magliozzi, Alessandro; Di Vico, Ilaria; Carecchio, Miryam; Bonato, Giulia; Cilia, Roberto; Colucci, Fabiana; Tamma, Filippo; Caputo, Elena; Mostile, Giovanni; Arabia, Gennarina; Modugno, Nicola; Zibetti, Maurizio; Ceravolo, Maria Gabriella; Tambasco, Nicola; Cossu, Giovanni; Valzania, Franco; Manganotti, Paolo; Di Lazzaro, Vincenzo; Zappia, Mario; Fabbrini, Giovanni; Tinazzi, Michele; Tessitore, Alessandro; Duro, Giovanni; Di Fonzo, Alessio

Titolo:

Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease

Anno:

2024

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

PARKINSONISM & RELATED DISORDERS

ISSN Rivista:

1353-8020

N° Volume:

124

Numero o Fascicolo:

107023

Intervallo pagine:

1-8

Parole chiave:

Gaucher disease; Genetic; Glucocerebrosidase; Glycosphingolipids; Parkinson's disease

Breve descrizione dei contenuti:

Introduction: Gaucher's disease (GD) is caused by biallelic mutations in the GBA1 gene, leading to reduced glucocerebrosidase (GCase) activity and substrate (glucosylceramide and glucosylsphingosine, GlcSph) accumulation. GBA1 variant carriers are at risk of Parkinson's disease (PD), but only those with biallelic mutations cross the threshold of GCase reduction, leading to substrate accumulation and GD. The link between GBA1 mutations, GD and PD is not fully understood. Here we aimed at reporting the results of a large PD population screening with dried blood spot tests for GD. Methods: We measured GCase activity and GlcSph levels in 1344 PD patients with dried blood spot tests, and performed GBA1 genetic sequencing. Results: While the GCase activity was reduced in GBA1-PD carriers compared to wild type PD, GlcSph was increased in GBA1-PD compared to GBA1-controls, regardless of the underlying type of GBA1 variant. 13.6 % and 0.4 % of PD patients had mono- or biallelic GBA1 mutations respectively. GCase deficiency, lipid accumulation and clinical manifestations of GD was detected in five PD patients with biallelic GBA1 mutations, of whom four had a risk combined with a GD causing variant. Conclusions: GlcSph appearing higher in PD may represent a reliable biomarker of the disease and deserves to be further investigated. This study highlights the importance of screening PD patients for possible underlying GD, which is a treatable condition that should not be missed. We diagnosed GD cases carrying a "risk" variant in one allele, which is an unprecedented finding deserving further investigation.

Pagina Web:

https://doi.org/10.1016/j.parkreldis.2024.107023

Id prodotto:

140037

Handle IRIS:

11562/1128388

ultima modifica:

22 agosto 2024

Citazione bibliografica:

Marano, Massimo; Zizzo, Carmela; Malaguti, Maria Chiara; Bacchin, Ruggero; Cavallieri, Francesco; De Micco, Rosa; Spagnolo, Francesca; Bentivoglio, Anna Rita; Schirinzi, Tommaso; Bovenzi, Roberta; Ramat, Silvia; Erro, Roberto; Sorrentino, Cristiano; Sucapane, Patrizia; Pilotto, Andrea; Lupini, Alessandro; Magliozzi, Alessandro; Di Vico, Ilaria; Carecchio, Miryam; Bonato, Giulia; Cilia, Roberto; Colucci, Fabiana; Tamma, Filippo; Caputo, Elena; Mostile, Giovanni; Arabia, Gennarina; Modugno, Nicola; Zibetti, Maurizio; Ceravolo, Maria Gabriella; Tambasco, Nicola; Cossu, Giovanni; Valzania, Franco; Manganotti, Paolo; Di Lazzaro, Vincenzo; Zappia, Mario; Fabbrini, Giovanni; Tinazzi, Michele; Tessitore, Alessandro; Duro, Giovanni; Di Fonzo, Alessio, Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease «PARKINSONISM & RELATED DISORDERS» , vol. 124 , n. 107023 , 2024 , pp. 1-8

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