Reduced glucocerebrosidase activity in monocytes from patients with Parkinson's disease

被引：86

作者：

Atashrazm, Farzaneh ^{[1
,2
]}

Hammond, Deborah ^{[1
,3
]}

Perera, Gayathri ^{[1
,2
]}

Dobson-Stone, Carol ^{[1
,5
]}

Mueller, Nicole ^{[1
,2
]}

Pickford, Russell ^{[4
]}

Kim, Woojin Scott ^{[1
,2
,5
]}

Kwok, John B. ^{[1
,5
]}

Lewis, Simon J. G. ^{[3
]}

Halliday, Glenda M. ^{[1
,2
,5
]}

Dzamko, Nicolas ^{[1
,2
,5
]}

机构：

[1] Univ Sydney, Brain & Mind Ctr, Cent Clin Sch, Camperdown, NSW 2050, Australia

[2] Neurosci Res Australia, Randwick, NSW 2031, Australia

[3] Univ Sydney, Brain & Mind Ctr, Forefront Parkinsons Dis Res Clin, Camperdown, NSW 2050, Australia

[4] Univ NSW, Bioanalyt Mass Spectrometry Facil, Kensington, NSW 2052, Australia

[5] Univ NSW, Sch Med Sci, Kensington, NSW 2052, Australia

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

FLOW-CYTOMETRIC ASSAY; ALPHA-SYNUCLEIN; GAUCHER-DISEASE; MUTATIONS; GENE; ACCUMULATION; DEFICIENCY; CELLS; MULTICENTER; LIPIDOMICS;

D O I：

10.1038/s41598-018-33921-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Missense mutations in glucocerebrosidase (GBA1) that impair the activity of the encoded lysosomal lipid metabolism enzyme (GCase) are linked to an increased risk of Parkinson's disease. However, reduced GCase activity is also found in brain tissue from Parkinson's disease patients without GBA1 mutations, implicating GCase dysfunction in the more common idiopathic form of Parkinson's disease. GCase is very highly expressed in monocytes, and thus we measured GCase activity in blood samples from recently diagnosed Parkinson's disease patients. Flow cytometry and immunoblotting assays were used to measure levels of GCase activity and protein in monocytes and lymphocytes from patients with Parkinson's disease (n = 48) and matched controls (n =44). Gene sequencing was performed to screen participants for GBA1 missense mutations. In the Parkinson's disease patients, GCase activity was significantly reduced in monocytes, but not lymphocytes, compared to controls, even when GBA1 mutation carriers were excluded. Monocyte GCase activity correlated with plasma ceramide levels in the Parkinson's disease patients. Our results add to evidence for GCase dysfunction in idiopathic Parkinson's disease and warrant further work to determine if monocyte GCase activity associates with Parkinson's disease progression.

引用

页数：12

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