Learn. Mem.：蛋白质对记忆形成有重要影响
生物谷报道：美国研究人员最近发现了一种蛋白酶，这种蛋白酶大脑神经元中的分布可能对记忆的形成有重要影响。
海马体是大脑里与记忆的编码、储存相关的区域。神经元间的神经键（即神经元之间的连接）对记忆影响很大，因为每个神经元至少与1000个其它神经元相连接。
研究人员通过检测老鼠海马体的神经元，确定了这些连接的强度，然后研究了蛋白质退化是如何影响连接强度的。蛋白质水平是由分布在所有细胞中的圆柱状的蛋白酶体所控制的。
此项研究首次表明，分布在神经元不同位置的蛋白酶体在控制神经键强度以及记忆方面发挥不同作用，这样研究将有助于治疗老年痴呆症等疾病。（生物谷www.bioon.com）
生物谷推荐原始出处：
LEARNING & MEMORY, May 2008; 15: 335 - 347.
Proteasome inhibition enhances the induction and impairs the maintenance of late-phase long-term potentiation
Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA
Protein degradation by the ubiquitin–proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity. We show here that inhibition of the proteasome enhances the induction of L-LTP, but inhibits its maintenance. Proteasome inhibitor-mediated enhancement of the early part of L-LTP requires activation of NMDA receptors and the cAMP-dependent protein kinase. Augmentation of L-LTP induction by proteasome inhibition is blocked by a protein synthesis inhibitor anisomycin and is sensitive to the drug rapamycin. Our findings indicate that proteasome inhibition increases the induction of L-LTP by stabilizing locally translated proteins in dendrites. In addition, our data show that inhibition of the proteasome blocks transcription of brain-derived neurotrophic factor (BDNF), which is a cAMP-responsive element-binding protein (CREB)-inducible gene. Furthermore, our results demonstrate that the proteasome inhibitors block degradation of ATF4, a CREB repressor. Thus, proteasome inhibition appears to hinder CREB-mediated transcription. Our results indicate that blockade of proteasome activity obstructs the maintenance of L-LTP by interfering with transcription as well as translation required to sustain L-LTP. Thus, proteasome-mediated proteolysis has different roles during the induction and the maintenance of L-LTP.
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