کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10869841 1073973 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A role of astrocytes in mediating postnatal neurodegeneration in Glutaric acidemia-type 1
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
A role of astrocytes in mediating postnatal neurodegeneration in Glutaric acidemia-type 1
چکیده انگلیسی
Astrocytes are crucial for postnatal development of neuronal networks, axon myelination and neurovascular structures. Defects in astrocyte generation or maturation are associated with severe neurological developmental disorders. Glutaric acidemia type I (GAI), an inherited neurometabolic disorder characterized by accumulation of glutaric (GA) and 3-hydroxyglutaric acids, shows a paradigmatic postnatal neuropathology characterized by massive degeneration of neurons in the striatum. While the disorder is caused by genetic mutations on glutaryl-CoA dehydrogenase, the neurological defects usually start months after birth. Pathogenesis of GAI has remained largely unknown, and specifically, it is unclear how accumulation of GAI metabolites may result in neurodegeneration. Recent evidence supports a GAI model involving primary defective astrocyte maturation leading to a co-morbid spectrum of neurologic symptoms similar to those of patients. Astrocytes are vulnerable to GAI metabolites, but instead of dying, they follow long-lasting phenotypic changes leading to striatal neuron degeneration as well as defective myelination and blood brain barrier maturation. Here, we summarized recent findings on the pathogenic role of GA-damaged astrocytes in GAI and discuss if astrocyte dysfunction may be a target of therapeutic interventions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 589, Issue 22, 14 November 2015, Pages 3492-3497
نویسندگان
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