کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5506709 | 1400302 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
LRRK2 deficiency impacts ceramide metabolism in brain
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: LRRK2 deficiency impacts ceramide metabolism in brain LRRK2 deficiency impacts ceramide metabolism in brain](/preview/png/5506709.png)
چکیده انگلیسی
Mutations in LRRK2 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 membrane-related 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 Lrrk2â/â mouse brains. In particular, we observe a significant increase of Cer levels in Lrrk2â/â 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 478, Issue 3, 23 September 2016, Pages 1141-1146
Journal: Biochemical and Biophysical Research Communications - Volume 478, Issue 3, 23 September 2016, Pages 1141-1146
نویسندگان
Ruggero Ferrazza, Susanna Cogo, Heather Melrose, Luigi Bubacco, Elisa Greggio, Graziano Guella, Laura Civiero, Nicoletta Plotegher,