کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021703 | 1580650 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Improvement of biochemical and behavioral defects in the Niemann-Pick type A mouse by intraventricular infusion of MARCKS
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
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چکیده انگلیسی
Niemann-Pick disease type A (NPDA) is a fatal disease due to mutations in the acid sphingomyelinase (ASM) gene, which triggers the abnormal accumulation of sphingomyelin (SM) in lysosomes and the plasma membrane of mutant cells. Although the disease affects multiple organs, the impact on the brain is the most invalidating feature. The mechanisms responsible for the cognitive deficit characteristic of this condition are only partially understood. Using mice lacking the ASM gene (ASMko), a model system in NPDA research, we report here that high sphingomyelin levels in mutant neurons lead to low synaptic levels of phosphoinositide PI(4,5)P2 and reduced activity of its hydrolyzing phosphatase PLCγ, which are key players in synaptic plasticity events. In addition, mutant neurons have reduced levels of membrane-bound MARCKS, a protein required for PI(4,5)P2 membrane clustering and hydrolysis. Intracerebroventricular infusion of a peptide that mimics the effector domain of MARCKS increases the content of PI(4,5)P2 in the synaptic membrane and ameliorates behavioral abnormalities in ASMko mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 73, January 2015, Pages 319-326
Journal: Neurobiology of Disease - Volume 73, January 2015, Pages 319-326
نویسندگان
Laura Trovò, Stijn Stroobants, Rudi D'Hooge, Maria Dolores Ledesma, Carlos G. Dotti,