早衰蛋白基因在遺傳上已被與家族性阿爾茨海默氏癥聯(lián)系起來,，但它們?cè)谑裁吹胤桨l(fā)揮作用,、它們?cè)谏窠?jīng)元中做什么卻不清楚,。
研究人員通過小鼠模型發(fā)現(xiàn)，早衰蛋白在突觸前腔中發(fā)揮作用,，控制依賴于活性的神經(jīng)傳輸物質(zhì)的釋放,，這是一個(gè)對(duì)于神經(jīng)計(jì)算、學(xué)習(xí)和記憶來說必不可少的過程。這些發(fā)現(xiàn)表明,，突觸前功能喪失也許是神經(jīng)退化性疾病中導(dǎo)致癡呆的一個(gè)早期原因,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 460, 632-636 (30 July 2009) | doi:10.1038/nature08177
Presenilins are essential for regulating neurotransmitter release
Chen Zhang1,2, Bei Wu1, Vassilios Beglopoulos1, Mary Wines-Samuelson1, Dawei Zhang1, Ioannis Dragatsis3, Thomas C. Südhof2 & Jie Shen1
1 Center for Neurologic Diseases, Brigham & Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
2 Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Palo Alto, California 94304, USA
3 Department of Physiology, The University of Tennessee, Health Science Center, Memphis, Tennessee 38163, USA
Mutations in the presenilin genes are the main cause of familial Alzheimer's disease. Loss of presenilin activity and/or accumulation of amyloid-peptides have been proposed to mediate the pathogenesis of Alzheimer's disease by impairing synaptic function1, 2, 3, 4, 5. However, the precise site and nature of the synaptic dysfunction remain unknown. Here we use a genetic approach to inactivate presenilins conditionally in either presynaptic (CA3) or postsynaptic (CA1) neurons of the hippocampal Schaeffer-collateral pathway. We show that long-term potentiation induced by theta-burst stimulation is decreased after presynaptic but not postsynaptic deletion of presenilins. Moreover, we found that presynaptic but not postsynaptic inactivation of presenilins alters short-term plasticity and synaptic facilitation. The probability of evoked glutamate release, measured with the open-channel NMDA (N-methyl-d-aspartate) receptor antagonist MK-801, is reduced by presynaptic inactivation of presenilins. Notably, depletion of endoplasmic reticulum Ca2+ stores by thapsigargin, or blockade of Ca2+ release from these stores by ryanodine receptor inhibitors, mimics and occludes the effects of presynaptic presenilin inactivation. Collectively, these results indicate a selective role for presenilins in the activity-dependent regulation of neurotransmitter release and long-term potentiation induction by modulation of intracellular Ca2+ release in presynaptic terminals, and further suggest that presynaptic dysfunction might be an early pathogenic event leading to dementia and neurodegeneration in Alzheimer's disease.
