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A peroxisome biogenesis deficiency prevents the binding of alpha-synuclein to lipid droplets in lipid-loaded yeast.

ABSTRACT: Using a yeast model of Parkinson's disease, we found that alpha-synuclein (?S) binds to lipid droplets in lipid-loaded, wild-type yeast cells but not to lipid droplets in lipid-loaded, peroxisome-deficient cells (pex3?). Our analysis revealed that pex3? cells have both fewer lipid droplets and smaller lipid droplets than wild-type cells, and that the acyl chains of the phospholipids on the surface of the lipid droplets from pex3? cells are on average shorter (C16) than those (C18) on the surface of lipid droplets from wild-type cells. We propose that the shift to shorter (C18?C16) acyl chains contributes to the reduced binding of ?S to lipid droplets in pex3? cells.

SUBMITTER: Wang S

PROVIDER: S-EPMC3770730 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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A peroxisome biogenesis deficiency prevents the binding of alpha-synuclein to lipid droplets in lipid-loaded yeast.

Wang Shaoxiao S Horn Patrick J PJ Liou Liang-Chun LC Muggeridge Martin I MI Zhang Zhaojie Z Chapman Kent D KD Witt Stephan N SN

Biochemical and biophysical research communications 20130731 2

Using a yeast model of Parkinson's disease, we found that alpha-synuclein (αS) binds to lipid droplets in lipid-loaded, wild-type yeast cells but not to lipid droplets in lipid-loaded, peroxisome-deficient cells (pex3Δ). Our analysis revealed that pex3Δ cells have both fewer lipid droplets and smaller lipid droplets than wild-type cells, and that the acyl chains of the phospholipids on the surface of the lipid droplets from pex3Δ cells are on average shorter (C16) than those (C18) on the surface ...[more]

PMID: 23916615

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Project description:Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss. Yet, the genes that connect beneficial environmental cues to the genome and delay disease-related symptoms have remained largely unclear. To identify such mediator genes, we used a 2 × 2 factorial design opposing genotype and environment. Specifically, we compared wildtype to transgenic mice overexpressing human SNCA, a key gene in synucleinopathies encoding alpha-synuclein, and housed them in a standard and enriched environment from weaning to 12 months of age before profiling their hippocampal transcriptome using RNA-sequencing. Under standard environmental conditions, differentially expressed genes were overrepresented for calcium ion binding, membrane, synapse, and other Gene Ontology terms previously linked to alpha-synuclein biology. Upregulated genes were significantly enriched for genes attributed to astrocytes, microglia, and oligodendrocytes. These disturbances in gene activity were accompanied by reduced levels of several presynaptic proteins and the immediate early genes EGR1 and NURR1. Intriguingly, housing transgenic animals in the enriched environment prevented most of these perturbations in gene activity. In addition, a sustained activation specifically in transgenic animals housed in enriched conditions was observed for several immediate early genes including Egr1, Nr4a2/Nurr1, Arc, and Homer1a. These findings suggest a compensatory mechanism through an enriched environment-activated immediate early gene network that prevented most disturbances induced by alpha-synuclein overexpression. This regulatory framework might harbor attractive targets for novel therapeutic approaches that mimic beneficial environmental stimuli.

Dataset Information

A peroxisome biogenesis deficiency prevents the binding of alpha-synuclein to lipid droplets in lipid-loaded yeast.

Publications

A peroxisome biogenesis deficiency prevents the binding of alpha-synuclein to lipid droplets in lipid-loaded yeast.

Similar Datasets

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