Neuronal Cx3cr1 Deficiency Protects against Amyloid β-Induced Neurotoxicity.
Neuronal Cx3cr1 Deficiency Protects against Amyloid β-Induced Neurotoxicity.
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DOI：
10.1371/journal.pone.0127730
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Murphy PM
中科院分区：
文献类型：
--
作者：
Dworzak J;Renvoisé B;Habchi J;Yates EV;Combadière C;Knowles TP;Dobson CM;Blackstone C;Paulsen O;Murphy PM
趋化因子Cx3cl1(Fractalkine)的受体CX3CR1与小鼠阿尔茨海默病样病理的进展和严重程度有关，但其潜在机制尚不清楚。一个复杂的因素是，CX3CR1在神经元和小胶质细胞中都有表达。在这里，我们剖析了神经元和小胶质细胞CX3CR1之间的差异，特别是通过比较直接淀粉样蛋白β对培养的、成熟的、去小胶质细胞的海马神经元的毒性，来自野生型和CX3CR1-/-小鼠。野生型神经元同时表达Cx3cl1和Cx3CR1，并释放Cx3cl1作为对淀粉样蛋白β的反应。神经元CX3CR1基因敲除可抑制淀粉样蛋白β诱导的乳酸脱氢酶释放。此外，淀粉样蛋白-β以一种多肽构象依赖的方式不同地诱导微小兴奋性突触后电流的突触前和突触后成分的抑制。神经元CX3CR1的敲除减弱了两种淀粉样蛋白-β构象状态的影响，这两种构象状态可以通过聚集动力学和肽形态来区分。我们用CX3CR1拮抗剂F1对培养的神经元进行急性和慢性处理后，得到了类似的结果。因此，神经元CX3CR1可能通过调节构象状态依赖的淀粉样蛋白β诱导的突触毒性来影响阿尔茨海默病样病理。
Cx3cr1, the receptor for the chemokine Cx3cl1 (fractalkine), has been implicated in the progression and severity of Alzheimer’s disease-like pathology in mice, but the underlying mechanisms remain unclear. A complicating factor is that Cx3cr1 has been demonstrated in both neurons and microglia. Here, we have dissected the differences between neuronal and microglial Cx3cr1, specifically by comparing direct amyloid-β-induced toxicity in cultured, mature, microglia-depleted hippocampal neurons from wild-type and Cx3cr1-/- mice. Wild-type neurons expressed both Cx3cl1 and Cx3cr1 and released Cx3cl1 in response to amyloid-β. Knockout of neuronal Cx3cr1 abated amyloid-β-induced lactate dehydrogenase release. Furthermore, amyloid-β differentially induced depression of pre- and postsynaptic components of miniature excitatory postsynaptic currents, in a peptide conformation-dependent manner. Knockout of neuronal Cx3cr1 abated effects of both amyloid-β conformational states, which were differentiable by aggregation kinetics and peptide morphology. We obtained similar results after both acute and chronic treatment of cultured neurons with the Cx3cr1 antagonist F1. Thus, neuronal Cx3cr1 may impact Alzheimer’s disease-like pathology by modulating conformational state-dependent amyloid-β-induced synaptotoxicity.
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DOI：
10.1523/jneurosci.4403-10.2010
发表时间：
2010-12-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liu Z;Condello C;Schain A;Harb R;Grutzendler J
通讯作者：
Grutzendler J
与次级途径成核聚合。 I.主要时刻的时间演变。
DOI：
10.1063/1.3608916
发表时间：
2011-08-14
期刊：
The Journal of chemical physics
影响因子：
--
作者：
Cohen SI;Vendruscolo M;Welland ME;Dobson CM;Terentjev EM;Knowles TP
通讯作者：
Knowles TP
影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
影响因子：
3.9
作者：
Cizas, Paulius;Budvytyte, Rima;Morkuniene, Ramune;Moldovan, Radu;Broccio, Matteo;Loesche, Mathias;Niaura, Gediminas;Valincius, Gintaras;Borutaite, Vilmante
通讯作者：
Borutaite, Vilmante
影响因子：
5.5
作者：
Dorgham, Karim;Ghadiri, Ata;Deterre, Philippe
通讯作者：
Deterre, Philippe