生物谷報(bào)道：美國研究人員最近發(fā)現(xiàn)了一種蛋白酶,，這種蛋白酶大腦神經(jīng)元中的分布可能對(duì)記憶的形成有重要影響,。
海馬體是大腦里與記憶的編碼,、儲(chǔ)存相關(guān)的區(qū)域。神經(jīng)元間的神經(jīng)鍵（即神經(jīng)元之間的連接）對(duì)記憶影響很大，因?yàn)槊總€(gè)神經(jīng)元至少與1000個(gè)其它神經(jīng)元相連接,。
研究人員通過檢測(cè)老鼠海馬體的神經(jīng)元，確定了這些連接的強(qiáng)度,，然后研究了蛋白質(zhì)退化是如何影響連接強(qiáng)度的,。蛋白質(zhì)水平是由分布在所有細(xì)胞中的圓柱狀的蛋白酶體所控制的。
此項(xiàng)研究首次表明,，分布在神經(jīng)元不同位置的蛋白酶體在控制神經(jīng)鍵強(qiáng)度以及記憶方面發(fā)揮不同作用,，這樣研究將有助于治療老年癡呆癥等疾病。（生物谷www.bioon.com）
生物谷推薦原始出處：
LEARNING & MEMORY, May 2008; 15: 335 - 347.
Proteasome inhibition enhances the induction and impairs the maintenance of late-phase long-term potentiation
Chenghai Dong1, Sudarshan C. Upadhya1, Lan Ding, Thuy K. Smith, and Ashok N. Hegde2
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.
