早衰蛋白基因在遗传上已被与家族性阿尔茨海默氏症联系起来，但它们在什么地方发挥作用、它们在神经元中做什么却不清楚。
Zhang等人通过小鼠模型发现，早衰蛋白在突触前腔中发挥作用，控制依赖于活性的神经传输物质的释放，这是一个对于神经计算、学习和记忆来说必不可少的过程。这些发现表明，突触前功能丧失也许是神经退化性疾病中导致痴呆的一个早期原因。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
