کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6022633 1580678 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Selective knockdown of mutant SOD1 in Schwann cells ameliorates disease in G85R mutant SOD1 transgenic mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Selective knockdown of mutant SOD1 in Schwann cells ameliorates disease in G85R mutant SOD1 transgenic mice
چکیده انگلیسی

Mutants of superoxide dismutase type 1 (mtSOD1) that have full dismutase activity (e.g., G37R) as well as none (e.g., G85R) cause familial amyotrophic lateral sclerosis (FALS), indicating that mtSOD1-induced FALS results from a toxicity rather than loss in SOD1 enzymatic activity. Still, it has remained unclear whether mtSOD1 dismutase activity can influence disease. A previous study demonstrated that Cre-mediated knockdown of G37R expression in Schwann cells (SCs) of G37R transgenic mice shortened the late phase of disease and survival. These results suggested that the neuroprotective effect of G37R expressed in SCs was greater than its toxicity, presumably because its dismutase activity counteracted reactive oxygen species (ROS). In order to further investigate this, we knocked down G85R in SCs by crossing G85Rflox mice with myelin-protein-zero (P0):Cre mice, which express Cre recombinase in SCs. Knockdown of G85R in SCs of G85R mice delayed disease onset and extended survival indicating that G85R expression in SCs is neurotoxic. These results demonstrate differences in the effect on disease of dismutase active vs. inactive mtSOD1 suggesting that both a loss as well as gain in function of mtSOD1 influence FALS pathogenesis. The results suggest that mtSOD1-induced FALS treatment may have to be adjusted depending on the cell type targeted and particular mtSOD1 involved.

► We knocked down dismutase-inactive G85R in Schwann cells in G85R transgenic mice. ► Expression of dismutase active vs. inactive mutant SOD1s in Schwann cells has different effects on FALS pathology. ► Loss and gain of function mechanisms associated with mutant SOD1 expression in Schwann cells modulate FALS disease. ► Reactive oxygen species and the Schwann cell are important targets for treatment of FALS. ► FALS treatment may have to be adjusted depending on the cell type targeted and particular mtSOD1 involved.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 48, Issue 1, October 2012, Pages 52-57
نویسندگان
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