期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 478, 期 3, 页码 1141-1146出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.08.082
关键词
Lipidomics; Sphingolipids; Parkinson ' s disease; Glucocerebrosidase; Gaucher ' s disease; Mass spectrometry
资金
- Michael J. Fox Foundation and Unipd
- Centre for Integrative Biology (CIBIO) Italy (RF)
- Marie Sklodowska-Curie Individual Fellowship [653434]
- Marie Curie Actions (MSCA) [653434] Funding Source: Marie Curie Actions (MSCA)
Mutations in gene cause inherited Parkinson's disease (PD) and variations around LRRK2 act as risk factor for disease. Similar to sporadic disease, LRRK2-linked cases show late onset and, typically, the presence of proteinaceous inclusions named Lewy bodies (LBs) in neurons. Recently, defects on ceramide (Cer) metabolism have been recognized in PD. In particular, heterozygous mutations in the gene encoding for glucocerebrosidase (GBA1), a lysosomal enzyme converting glucosyl-ceramides (Glc-Cer) into Cer, increase the risk of developing PD. Although several studies have linked LRRK2 with membranerelated processes and autophagic-lysosomal pathway regulation, whether this protein impinges on the Cer pathway has not been addressed. Here, using a targeted lipidomics approach, we report an altered sphingolipid composition in Lrrk2(-/-) mouse brains. In particular, we observe a significant increase of Cer levels in Lrrk2 (-/-) mice and direct effects on GBA1. Collectively, our results suggest a link between LRRK2 and Cer metabolism, providing new insights into the possible role of this protein in sphingolipids metabolism, with implications for PD therapeutics. (C) 2016 Elsevier Inc. All rights reserved.
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