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Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain
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نویسنده
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wang k. ,xu r. ,schrandt j. ,shah p. ,gong y.z. ,preston c. ,wang l. ,yi j.k. ,lin c.-l. ,sun w. ,spyropoulos d.d. ,rhee s. ,li m. ,zhou j. ,ge s. ,zhang g. ,snider a.j. ,hannun y.a. ,obeid l.m. ,mao c.
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منبع
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plos genetics - 2015 - دوره : 11 - شماره : 10
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چکیده
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Dyshomeostasis of both ceramides and sphingosine-1-phosphate (s1p) in the brain has been implicated in aging-associated neurodegenerative disorders in humans. however,mechanisms that maintain the homeostasis of these bioactive sphingolipids in the brain remain unclear. mouse alkaline ceramidase 3 (acer3),which preferentially catalyzes the hydrolysis of c18:1-ceramide,a major unsaturated long-chain ceramide species in the brain,is upregulated with age in the mouse brain. acer3 knockout causes an age-dependent accumulation of various ceramides and c18:1-monohexosylceramide and abolishes the age-related increase in the levels of sphingosine and s1p in the brain; thereby resulting in purkinje cell degeneration in the cerebellum and deficits in motor coordination and balance. our results indicate that acer3 plays critically protective roles in controlling the homeostasis of various sphingolipids,including ceramides,sphingosine,s1p,and certain complex sphingolipids in the brain and protects purkinje cells from premature degeneration.
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آدرس
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department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny,united states,department of hepatobiliary surgery,nanfang hospital,southern medical university,guangzhou, China, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny, United States, division of rehabilitation sciences,department of physical therapy,school of health technology and management,stony brook university,stony brook,ny,united states,department of neurobiology and behavior,stony brook university,stony brook,ny, United States, medical university of south carolina,charleston,sc, United States, division of rehabilitation sciences,department of physical therapy,school of health technology and management,stony brook university,stony brook,ny, United States, division of rehabilitation sciences,department of physical therapy,school of health technology and management,stony brook university,stony brook,ny, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny, United States, medical university of south carolina,charleston,sc, United States, medical university of south carolina,charleston,sc, United States, medical university of south carolina,charleston,sc, United States, department of gastroenterology,nanfang hospital,southern medical university,guangzhou, China, department of hepatobiliary surgery,nanfang hospital,southern medical university,guangzhou, China, medical university of south carolina,charleston,sc, United States, biomedical engineering and physical science shared resource,national institute of biomedical imaging and bioengineering,national institute of health,bethesda,md, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny,united states,northport veterans affairs medical center,northport,ny, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny,united states,northport veterans affairs medical center,northport,ny, United States, department of medicine,stony brook university,stony brook,ny,united states,stony brook cancer center,stony brook,ny, United States
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Authors
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