脆性 X 症的病理生理学（及其对突触的启示）。
The pathophysiology of fragile X (and what it teaches us about synapses).
机构信息
Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Annu Rev Neurosci. 2012;35:417-43. doi: 10.1146/annurev-neuro-060909-153138. Epub 2012 Apr 5.
Abstract
Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way.
摘要
脆性 X 是最常见的已知遗传性智力障碍和自闭症病因，通常由 FMR1 的转录沉默和其编码蛋白 FMRP（脆性 X 智力低下蛋白）缺失导致。FMRP 是一种 mRNA 结合蛋白，在许多突触处发挥作用，抑制代谢型谷氨酸受体 (mGluR) 1 和 5 刺激的局部翻译。最近关于 FMRP 的生物学和 mGluR1/5 下游信号通路的研究深入了解了经验如何调节突触蛋白合成和可塑性。这些新知识还提示了如何纠正脆性 X 中的信号转导和突触功能异常，并且基于这些信息的人类临床试验正在进行中。
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