| 2 | Heterozygous carriers of galactocerebrosidase mutations that cause Krabbe disease have impaired microglial function and defective repair of myelin damage显示文摘This review addresses two puzzling findings related to mutations in galactocerebrosidase(GALC)that cause Krabbe disease(KD),a severe lysosomal storage disorder characterized by extensive myelin damage in children with mutations in both GALC alleles.First,heterozygous carriers of KD-causing mutations,which include the biological parents of children with KD,exhibit increased risk for developing other diseases.Second,variants in the GALC locus increase the risk of developing multiple sclerosis(MS),anothermice had striking defects in repair of cuprizone-induced damage.We further found unexpected microglial defects in myelin debris clearance and in the ability to up-regulate the Trem2 microglial protein critical formodel of KD.Thus,heterozygous GALC mutations cause effects on biological function that may help to understand the increased disease risk in heterozygous carriers of such mutations and to understand why GALC variations increase the risk of MS.Our findings indicate that while some genetic risk factors may contribute to complex diseases by increasing the risk of tissue damage,others may do so by compromising tissue repair. | Nicole J.Scott-Hewitt Christopher J.Folts Mark D.Noble | 2018 | Neural Regeneration Research2018，13，3： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员