Premium
Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations
Author(s) -
Pchelina Sofya,
Baydakova Galina,
Nikolaev Mikhael,
Senkevich Konstantin,
Emelyanov Anton,
Kopytova Alena,
Miliukhina Irina,
Yakimovskii Andrey,
Timofeeva Alla,
Berkovich Olga,
Fedotova Ekatrina,
Illarioshkin Sergey,
Zakharova Ekaterina
Publication year - 2018
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27393
Subject(s) - glucocerebrosidase , glucocerebroside , sphingomyelin , parkinson's disease , medicine , enzyme , endocrinology , disease , chemistry , biochemistry , cholesterol
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