The emergence of Parkinson disease among patients with Gaucher disease

Elstein, Deborah; Alcalay, Roy N.; Zimran, Ari

doi:10.1016/j.beem.2014.08.007

Cited by 14 publications

(11 citation statements)

References 73 publications

(67 reference statements)

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“…2 Three phenotypes (1-3) of GD have been defined by the presence (types 2 and 3) or absence (type 1) of early-onset progressive CNS involvement. [2][3][4] Type 2 GD presents in infancy, usually leading to death within 1-3 years of onset, while type 3 patients generally experience a later involvement of the CNS, often surviving for several decades. Although type 1 GD patients experience a highly variable visceral disease and typically remain free of CNS involvement, they have a much greater lifetime risk of developing Parkinson's disease and Lewy body disease.…”

Section: Introductionmentioning

confidence: 99%

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry

Jones¹,

Zhang

Zhao

et al. 2017

SLAS Discovery

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To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS. MALDI IMS detected several HexCers across the brains. Comparison with the brain hematoxylin and eosin (H&E) revealed differential signal distributions in the midbrain, brain stem, and CB of the GD brain versus the control. Quantitation of serial brain sections with LC-ESI-MS/MS supported the imaging results, finding the overall HexCer levels in the 4L/PS-NA brains to be four times higher than the control. LC-ESI-MS/MS also confirmed that the elevated hexosyl isomers were glucosylceramides rather than galactosylceramides. MALDI imaging also detected differential analyte distributions of lactosylceramide species and gangliosides in the 4L/PS-NA brain, which was validated by LC-ESI-MS/MS. Immunohistochemistry revealed regional inflammation, altered autophagy, and defective protein degradation correlating with regions of GSL accumulation, suggesting that specific GSLs may have distinct neuropathological effects.

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Section: Introductionmentioning

confidence: 99%

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry

Jones¹,

Zhang

Zhao

et al. 2017

SLAS Discovery

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“…ND, not determined. a Carbon number and degree of unsaturation of N-acyl chain in the ceramide moiety (e.g., 16:0 for fatty acyl chain with 16 carbons and zero double bonds). The mean values are the ratios of GlcCer and GalCer species to GlcCer(d18:1/8:0) and GalCer(d18:1/8:0), respectively, from quadruplicate experiments.…”

Section: Discussionmentioning

confidence: 99%

“…CF, correction factor. a Carbon number and degree of unsaturation of N-fatty acyl chain in the ceramide moiety (e.g., 16:0 for fatty acyl chain with 16 carbons and zero double bonds). GalCer.…”

Section: Discussionmentioning

confidence: 99%

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DMS as an orthogonal separation to LC/ESI/MS/MS for quantifying isomeric cerebrosides in plasma and cerebrospinal fluid

Boucher

Nguyễn

et al. 2019

Journal of Lipid Research

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This article is available online at http://www.jlr.org an orthogonal separation to LC/ESI/MS/MS for quantifying isomeric cerebrosides in plasma and cerebrospinal fluid. J. Lipid Res. 2019. 60: 200-211.Supplementary key words lipidomics • liquid chromatography • mass spectrometry • tandem mass spectrometry • electrospray ionization • cerebrosides • sphingolipids • differential ion mobility spectrometry Glycosphingolipids (GSLs) are essential plasma membrane lipid components of eukaryotes. Together with cholesterol and sphingomyelin, GSLs form microdomains on plasma membranes that play important roles in various cellular activities such as adhesion, growth, and differentiation (1). The simplest GSLs are monohexosylceramides (also known as cerebrosides). Cerebrosides are composed of a lipid, ceramide, that is embedded in the outer leaflet of the plasma membrane, and a sugar moiety, either glucose Abstract Cerebrosides, including glucosylceramides (GlcCers) and galactosylceramides (GalCers), are important membrane components of animal cells with deficiencies resulting in devastating lysosomal storage disorders. Their quantification is essential for disease diagnosis and a better understanding of disease mechanisms. The simultaneous quantification of GlcCer and GalCer isomers is, however, particularly challenging due to their virtually identical structures. To address this challenge, we developed a new LC/ MS-based method using differential ion mobility spectrometry (DMS) capable of rapidly and reproducibly separating and quantifying isomeric cerebrosides in a single run. We show that this LC/ESI/DMS/MS/MS method exhibits robust quantitative performance within an analyte concentration range of 2.8-355 nM. We further report the simultaneous quantification of nine GlcCers (16:0, 18:0, 20:0, 22:0, 23:0, 24:1, 24:0, 25:0, and 26:0) and five GalCers (16:0, 22:0, 23:0, 24:1, and 24:0) molecular species in human plasma, as well as six GalCers (18:0, 22:0, 23:0, 24:1, 24:0 and 25:0) and two GlcCers (24:1 and 24:0) in human cerebrospinal fluid. Our method expands the potential of DMS technology in the field of glycosphingolipid analysis for both biomarker discovery and drug screening by enabling the unambiguous assignment and quantification of cerebroside lipid species in biological samples

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“…ERT is based on the intravenous administration of recombinant GCase, which does not cross the blood-brain barrier [11]. SRT reduces the accumulation of glucosylceramide and can cross the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Parkinson disease in Gaucher disease

2017

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BackgroundGaucher disease (GD) is an inborn error of metabolism caused by mutations in the gene (GBA) coding for glucocerebrosidase (GCase), inherited in an autosomal recessive pattern. GD patients have up to 9% risk of developing PD.Case presentationWe report two patients with GD that developed PD at different disease stages.ConclusionWe reviewed the literature on the coexistence of PD and GD and speculate that the severity of symptoms may be related to the type of GBA mutation inherited.Electronic supplementary materialThe online version of this article (doi:10.1186/s40734-017-0054-2) contains supplementary material, which is available to authorized users.

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The emergence of Parkinson disease among patients with Gaucher disease

Cited by 14 publications

References 73 publications

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry

DMS as an orthogonal separation to LC/ESI/MS/MS for quantifying isomeric cerebrosides in plasma and cerebrospinal fluid

Parkinson disease in Gaucher disease

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