#Iina massini skin
The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0. PMID:28769867ĭirectory of Open Access Journals (Sweden)įull Text Available The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception.
Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Namer, Barbara Ørstavik, Kirstin Schmidt, Roland Mair, Norbert Kleggetveit, Inge Petter Zeidler, Maximillian Martha, Theresa Jorum, Ellen Schmelz, Martin Kalpachidou, Theodora Kress, Michaela Langeslag, Michiel These data suggest that Fabry disease may be amenable to substrate deprivation therapy.Ĭhanges in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg/kg twice daily, renal globotriaosylceramide fell to below starting levels, consistent with an alpha-galactosidase A-independent salvage pathway for globotriaosylceramide degradation. A concentration-dependent decrement in renal and hepatic globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P4.
A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidi no-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation.Ībe, A Gregory, S Lee, L Killen, P D Brady, R O Kulkarni, A Shayman, J A
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