Neurobiology of Disease Increasing Sulfatide Synthesis in Myelin-Forming Cells of Arylsulfatase A-Deficient Mice Causes Demyelination and Neurological Symptoms Reminiscent of Human Metachromatic Leukodystrophy
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چکیده
Hariharasubramanian Ramakrishnan,1* Kerstin Khalaj Hedayati,2* Renate Lüllmann-Rauch,2 Carsten Wessig,3 Simon Ngamli Fewou,1 Helena Maier,1 Hans-Hilmar Goebel,4 Volkmar Gieselmann,1 and Matthias Eckhardt1 1Institute of Physiological Chemistry, Rheinische Friedrich-Wilhelms University of Bonn, 53115 Bonn, Germany, 2Institute of Anatomy, Christian-Albrechts University of Kiel, 24098 Kiel, Germany, 3Department of Neurology, Julius-Maximilians University of Würzburg, 97080 Würzburg, Germany, and 4Department of Neuropathology, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany
منابع مشابه
Sulfatide storage in neurons causes hyperexcitability and axonal degeneration in a mouse model of metachromatic leukodystrophy.
Metachromatic leukodystrophy is a lysosomal storage disorder caused by deficiency in the sulfolipid degrading enzyme arylsulfatase A (ASA). In the absence of a functional ASA gene, 3-O-sulfogalactosylceramide (sulfatide; SGalCer) and other sulfolipids accumulate. The storage is associated with progressive demyelination and various finally lethal neurological symptoms. Lipid storage, however, is...
متن کاملMetachromatic leukodystrophy: genetics, pathogenesis and therapeutic options.
UNLABELLED Metachromatic leukodystrophy is a lysosomal storage disease caused by the deficiency of arylsulphatase A (ASA). This leads to storage of the membrane lipid sulphatide, which is abundant in myelin. A pathological hallmark of the disease is demyelination, causing various and ultimately lethal neurological symptoms. Today more than 110 mutations in the ASA gene have been identified, of ...
متن کاملIntracerebroventricular enzyme infusion corrects central nervous system pathology and dysfunction in a mouse model of metachromatic leukodystrophy.
Arylsulfatase A (ASA) catalyzes the desulfation of sulfatide, a major lipid component of myelin. Inherited functional deficiencies of ASA cause the lysosomal storage disease (LSD) metachromatic leukodystrophy (MLD), which is characterized by intralysosomal accumulation of sulfatide, progressive neurological symptoms and early death. Enzyme replacement therapy (ERT) using intravenous injection o...
متن کاملPhenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy.
Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store the sphingolipid cerebroside-3-sulfat...
متن کاملEfficacy of enzyme replacement therapy in an aggravated mouse model of metachromatic leukodystrophy declines with age.
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency of arylsulfatase A (ASA). Previous studies in ASA-knockout mice suggested enzyme replacement therapy (ERT) to be a promising treatment option. The mild phenotype of ASA-knockout mice did, however, not allow to examine therapeutic responses of the severe neurological symptoms that dominate MLD. We...
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تاریخ انتشار 2007