Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations.
Mov Disord
; 33(8): 1325-1330, 2018 08.
Article
en En
| MEDLINE
| ID: mdl-30192031
ABSTRACT
INTRODUCTION:
Glucocerebrosidase 1 mutations, the most common genetic contributor to Parkinson's disease (PD), have been associated with decreased glucocerebrosidase enzymatic activity in PD patients with glucocerebrosidase 1 mutations (glucocerebrosidase 1-PD). However, it is unknown whether this decrease in enzymatic activity leads to lysosphingolipid accumulations.METHODS:
The levels of hexosylsphingosines, globotriaosylsphingosine, sphingomyelin, and sphingomyelin-509 were measured in dried blood spots from glucocerebrosidase 1-PD patients (n = 23), sporadic PD patients (n = 105), Gaucher disease patients (n = 32), and controls (n = 88) by liquid chromatography-tandem mass spectrometry.RESULTS:
Glucocerebrosidase 1-PD patients had increased hexosylsphingosine levels when compared with sporadic PD patients (P < .001) and controls (P < .0001). Hexosylsphingosine levels were increased in glucocerebrosidase 1 mutation carriers of glucocerebrosidase 1 (L444P; N370S; n = 11, P = .001) and glucocerebrosidase 1 polymorphic variants (E326K, T369M) associated with PD (n = 12, P = .04) when compared with controls.CONCLUSIONS:
Lysosphingolipid accumulations in PD patients who bear glucocerebrosidase 1 mutations suggest that substrate reduction therapy might be viewed as a possible strategy for glucocerebrosidase 1-PD treatment. © 2018 International Parkinson and Movement Disorder Society.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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Esfingolípidos
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Glucosilceramidasa
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Mutación
Tipo de estudio:
Clinical_trials
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mov Disord
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article