NMDA 受体在阿尔茨海默病中的作用的新进展。
New developments on the role of NMDA receptors in Alzheimer's disease.
机构信息
Center for Neural Circuits and Behavior, Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093, USA.
出版信息
Curr Opin Neurobiol. 2012 Jun;22(3):559-63. doi: 10.1016/j.conb.2011.09.001. Epub 2011 Sep 29.
Abstract
Since the initial findings that NMDA receptors play important roles in cellular models of learning as well as neurotoxicity, abnormal function of this receptor has been considered a potential mechanism in the pathophysiology underlying Alzheimer's disease. Treatment of Alzheimer's disease with an NMDA receptor antagonist began several years ago, with some limited success. More recent mechanistic studies have examined the role of NMDA receptors in the synaptic effects of beta amyloid (Aβ).
摘要
自最初发现 NMDA 受体在学习和神经毒性的细胞模型中发挥重要作用以来，该受体的异常功能已被认为是阿尔茨海默病病理生理学的潜在机制。几年前，开始使用 NMDA 受体拮抗剂治疗阿尔茨海默病，取得了一定的成效。最近的机制研究检查了 NMDA 受体在β淀粉样蛋白（Aβ）的突触效应中的作用。
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本文引用的文献
1
Opposing synaptic regulation of amyloid-β metabolism by NMDA receptors in vivo.体内 NMDA 受体对淀粉样蛋白-β代谢的突触调节作用相反。
J Neurosci. 2011 Aug 3;31(31):11328-37. doi: 10.1523/JNEUROSCI.0607-11.2011.
2
Aβ(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β.β淀粉样蛋白（1-42）抑制 LTP 是通过一种涉及半胱天冬酶-3、Akt1 和 GSK-3β的信号通路介导的。
Nat Neurosci. 2011 May;14(5):545-7. doi: 10.1038/nn.2785. Epub 2011 Mar 27.
3
Amyloid β peptide oligomers directly activate NMDA receptors.淀粉样β肽寡聚体直接激活 NMDA 受体。
Cell Calcium. 2011 Mar;49(3):184-90. doi: 10.1016/j.ceca.2011.02.001. Epub 2011 Feb 23.
4
Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of β-amyloid oligomers on long-term potentiation (LTP) in murine hippocampal slices.NR2B 含 NMDA 受体和 mGluR5 代谢型谷氨酸受体在介导 β-淀粉样寡聚体对小鼠海马切片长时程增强（LTP）的突触毒性作用中的治疗意义。
Neuropharmacology. 2011 May;60(6):982-90. doi: 10.1016/j.neuropharm.2011.01.051. Epub 2011 Feb 12.
5
Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration.tau 蛋白向树突棘的定位错误介导了突触功能障碍，而与神经退行性变无关。
Neuron. 2010 Dec 22;68(6):1067-81. doi: 10.1016/j.neuron.2010.11.030.
6
Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease.Caspase-3 引发阿尔茨海默病小鼠模型中的早期突触功能障碍。
Nat Neurosci. 2011 Jan;14(1):69-76. doi: 10.1038/nn.2709. Epub 2010 Dec 12.
7
Reversing EphB2 depletion rescues cognitive functions in Alzheimer model.逆转 EphB2 耗竭可挽救阿尔茨海默病模型中的认知功能。
Nature. 2011 Jan 6;469(7328):47-52. doi: 10.1038/nature09635. Epub 2010 Nov 28.
8
Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-ß production.非突触型 NMDA 受体的激活改变了淀粉样前体蛋白的表达模式，并增加了淀粉样-β的产生。
J Neurosci. 2010 Nov 24;30(47):15927-42. doi: 10.1523/JNEUROSCI.3021-10.2010.
9
Amyloid-β induces caspase-dependent loss of PSD-95 and synaptophysin through NMDA receptors.淀粉样β通过 NMDA 受体诱导 PSD-95 和突触小泡蛋白依赖半胱天冬酶的丢失。
J Alzheimers Dis. 2010;22(2):541-56. doi: 10.3233/JAD-2010-100948.
10
Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models.tau 的树突功能介导阿尔茨海默病小鼠模型中的淀粉样β毒性。
Cell. 2010 Aug 6;142(3):387-97. doi: 10.1016/j.cell.2010.06.036. Epub 2010 Jul 22.
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