MovDisordV3, Main, Exploration, bibRecord, 000667

Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson’s disease.

Identifieur interne : 000667 ( Main/Exploration ); précédent : 000666; suivant : 000668

Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson’s disease.

Auteurs : Sarah K. Abbott ; Hongyun Li ; Sonia Sanz Mu Oz ; Bianca Knoch ; Marijka Batterham ; Karen E. Murphy ; Glenda M. Halliday ; Brett Garner

Source :

Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.

RBID : pubmed:24822250

English descriptors

KwdEn :
- Aged, Aged, 80 and over, Brain (metabolism), Brain (pathology), Ceramides (metabolism), Female, Gene Expression, Humans, Male, Middle Aged, Oxidoreductases (genetics), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology).
MESH :
- chemical , genetics : Oxidoreductases.
- chemical , metabolism : Ceramides.
- genetics : Parkinson Disease.
- metabolism : Brain, Parkinson Disease.
- pathology : Brain, Parkinson Disease.
- Aged, Aged, 80 and over, Female, Gene Expression, Humans, Male, Middle Aged.

Abstract

Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson’s disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case-control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD-associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase-1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics.

PubMed: 24822250

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson’s disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case-control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD-associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase-1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics.</div>
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<name sortKey="Li, Hongyun" sort="Li, Hongyun" uniqKey="Li H" first="Hongyun" last="Li">Hongyun Li</name>
<name sortKey="Mu Oz, Sonia Sanz" sort="Mu Oz, Sonia Sanz" uniqKey="Mu Oz S" first="Sonia Sanz" last="Mu Oz">Sonia Sanz Mu Oz</name>
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Movement Disorders (revue)

Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson’s disease.

Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson’s disease.

Source :

English descriptors

Abstract

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	Movement Disorders (revue)
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