کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039056 1073017 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation
ترجمه فارسی عنوان
دور زدن فارماکولوژیک تابع سندرم کوکین در تشخیص عصبی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Neuritogenesis defects in CS cell lines can be overcome by overexpression of SYT9
• SYT9 is crucial for neuritogenesis and involved in neurotrophin (BDNF) signaling
• Neuritogenesis defects in CS cell lines can be overcome by BDNF treatment
• They can also be overcome by treatment with amitriptyline, an FDA-approved BDNF mimic

SummaryCockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9), a key component of the machinery controlling neurotrophin release, bypasses the need for CSB in neuritogenesis. Importantly, brain-derived neurotrophic factor (BDNF), a neurotrophin implicated in neuronal differentiation and synaptic modulation, and pharmacological mimics such as 7,8-dihydroxyflavone and amitriptyline can compensate for CSB deficiency in cell models of neuronal differentiation as well. SYT9 and BDNF are downregulated in CS patient brain tissue, further indicating that sub-optimal neurotrophin signaling underlies neurological defects in CS. In addition to shedding light on cellular mechanisms underlying CS and pointing to future avenues for pharmacological intervention, these data suggest an important role for SYT9 in neuronal differentiation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 14, Issue 11, 22 March 2016, Pages 2554–2561
نویسندگان
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