کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6805577 | 1433564 | 2014 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
α-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy
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کلمات کلیدی
OligodendrogenesisMultiple system atrophy - آتروفی سیستم چندگانهAlpha-synuclein - آلفا سینوئولینMaturation - بلوغTransgenic - تراریختهDifferentiation - تفکیکMyelin basic protein - پروتئین پایه میلینplatelet derived growth factor receptor alpha - پلاکت عامل گیرنده عامل گیرنده آلفاOligodendrocyte precursors - پیش سازهای اولیگودندروسیت
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Multiple system atrophy (MSA), an atypical parkinsonian disorder, is characterized by α-synuclein (α-syn+) cytoplasmatic inclusions in mature oligodendrocytes. Oligodendrocyte progenitor cells (OPCs) represent a distinct cell population with the potential to replace dysfunctional oligodendrocytes. However, the role of OPCs in MSA and their potential to replace mature oligodendrocytes is still unclear. A postmortem analysis in MSA patients revealed α-syn within OPCs and an increased number of striatal OPCs. In an MSA mouse model, an age-dependent increase of dividing OPCs within the striatum and the cortex was detected. Despite of myelin loss, there was no reduction of mature oligodendrocytes in the corpus callosum or the striatum. Dissecting the underlying molecular mechanisms an oligodendroglial cell line expressing human α-syn revealed that α-syn delays OPC maturation by severely downregulating myelin-gene regulatory factor and myelin basic protein. Brain-derived neurotrophic factor was reduced in MSA models and its in vitro supplementation partially restored the phenotype. Taken together, efficacious induction of OPC maturation may open the window to restore glial and neuronal function in MSA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 35, Issue 10, October 2014, Pages 2357-2368
Journal: Neurobiology of Aging - Volume 35, Issue 10, October 2014, Pages 2357-2368
نویسندگان
Verena E.L. May, Benjamin Ettle, Anne-Maria Poehler, Silke Nuber, Kiren Ubhi, Edward Rockenstein, Beate Winner, Michael Wegner, Eliezer Masliah, Jürgen Winkler,