Serum lipid alterations in GBA-associated Parkinson's disease

Guedes, Leonor Correia; Chan, Robin B.; Gomes, Marcos António; Conceição, Vasco A.; Machado, Raquel; Soares, Tiago; Xu, Yimeng; Gaspar, Paulo; Carriço, João André; Alcalay, Roy N.; Ferreira, Joaquim J.; Outeiro, Tiago F.; Miltenberger-Miltényi, Gábriel

doi:10.1016/j.parkreldis.2017.08.026

Cited by 70 publications

(61 citation statements)

References 28 publications

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“…Major differences between the two studies are that our control cohort had a sample size of 44, compared to a control cohort size of 5, and that we have employed an advanced lipidomic strategy 39 , allowing the identification of 59 ceramide species compared to 9. More recently, plasma ceramide levels have also been reported as increased in PD patients carrying GBA1 mutations compared to PD patients without GBA1 mutations 40 . A comparison of plasma ceramide levels to controls was not performed in that study and we note that composition of the GBA1 mutation carrier group is substantially different to the mutation carriers we identified in the present study.…”

Section: Discussionmentioning

confidence: 96%

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

Atashrazm

Hammond

Perera

et al. 2018

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 96%

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

Atashrazm

Hammond

Perera

et al. 2018

Sci Rep

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“…23 A decrease in GCase activity along with elevated plasma oligomeric α-synuclein levels have been shown in the same cohort of GBA-PD patients previously. 10 A recent paper by Guedes and colleagues 24 reported lysoSLs accumulation in GBA mutation carriers. An elevation of monohexosylceramide, ceramide, and sphingomyelin was shown.…”

Section: Discussionmentioning

confidence: 97%

Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations

et al. 2018

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“…The glycerophospholipid PE has a structural role in biological membranes, and it is a regulator of cell division, membrane fusion/fission, and hepatic secretion of very low-density lipoproteins (VLDL) [267]. Patients with PD show decreased plasma levels of PE 34:2 [222], and those carrying a GBA mutation have decreased serum levels of PE compared to non- GBA mutation carriers [268]. Decreased total PE levels have also been observed in the SN of PD patients before treatment [269], in males only after treatment [270], and in the primary visual cortex [225].…”

Section: Glycerophospholipidsmentioning

confidence: 99%

The Role of Lipids in Parkinson’s Disease

Xicoy

Wieringa

Martens

2019

Cells

179

161

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by a progressive loss of dopaminergic neurons from the nigrostriatal pathway, formation of Lewy bodies, and microgliosis. During the past decades multiple cellular pathways have been associated with PD pathology (i.e., oxidative stress, endosomal-lysosomal dysfunction, endoplasmic reticulum stress, and immune response), yet disease-modifying treatments are not available. We have recently used genetic data from familial and sporadic cases in an unbiased approach to build a molecular landscape for PD, revealing lipids as central players in this disease. Here we extensively review the current knowledge concerning the involvement of various subclasses of fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and lipoproteins in PD pathogenesis. Our review corroborates a central role for most lipid classes, but the available information is fragmented, not always reproducible, and sometimes differs by sex, age or PD etiology of the patients. This hinders drawing firm conclusions about causal or associative effects of dietary lipids or defects in specific steps of lipid metabolism in PD. Future technological advances in lipidomics and additional systematic studies on lipid species from PD patient material may improve this situation and lead to a better appreciation of the significance of lipids for this devastating disease.

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Serum lipid alterations in GBA-associated Parkinson's disease

Cited by 70 publications

References 28 publications

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

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

Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations

The Role of Lipids in Parkinson’s Disease

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