Alzheimer's Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection.
Alzheimer's Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection.
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DOI：
10.1016/j.neuron.2018.06.030
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发表时间：
2018-07-11
期刊：
影响因子：
16.2
通讯作者：
Moir RD
中科院分区：
文献类型：
--
作者：
Eimer WA;Vijaya Kumar DK;Navalpur Shanmugam NK;Rodriguez AS;Mitchell T;Washicosky KJ;György B;Breakefield XO;Tanzi RE;Moir RD
淀粉样蛋白-β肽（Aβ）纤维化和β-淀粉样蛋白沉积是阿尔茨海默病（AD）病理的标志。我们最近报道了Aβ是一种先天免疫蛋白，可以防止真菌和细菌感染。纤化途径介导Aβ抗菌活性。因此，感染可以播种并显著加速β-淀粉样蛋白沉积。本研究表明，在5XFAD小鼠和3D人神经细胞培养感染模型中，Aβ寡聚物结合疱疹病毒表面糖蛋白，加速β-淀粉样蛋白沉积，并导致保护性病毒包裹活性，这些感染模型针对嗜神经性单纯疱疹病毒1 （HSV1）和人疱疹病毒6A和b。疱疹病毒与AD有关，但病毒如何诱导大脑β-淀粉样蛋白变性尚不清楚。这些数据支持了a β可能在中枢神经系统先天免疫中发挥保护作用的观点，并提示了疱疹病毒感染可能直接促进a β淀粉样变的AD病因机制。Eimer等人报道，Aβ将疱疹病毒困在一种叫做淀粉样蛋白的不溶性沉积物中。高淀粉样蛋白积累被认为是阿尔茨海默病病理的驱动因素。因此，本研究提示活动性脑疱疹感染可能加速淀粉样蛋白沉积和阿尔茨海默病的进展。
Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid are hallmarks of Alzheimer’s disease (AD) pathology. We recently reported Aβ is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate Aβ antimicrobial activities. Thus, infection can seed and dramatically accelerate β-amyloid deposition. Here, we show Aβ oligomers bind herpesvirus surface glycoproteins, accelerating β-amyloid deposition and leading to protective viral entrapment activity in 5XFAD mouse and 3D human neural cell culture infection models against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6A and B. Herpesviridae are linked to AD, but it has been unclear how viruses may induce β-amyloidosis in brain. These data support the notion that Aβ might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote Aβ amyloidosis. Eimer et al. report that Aβ traps herpes viruses in insoluble deposits called amyloid. High amyloid accumulation is known to drive Alzheimer’s disease pathology. Hence, this study suggests that active herpes infections in brain may accelerate amyloid deposition and the progression of Alzheimer’s disease.
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影响因子：
4
作者：
Bourgade, Karine;Le Page, Aurelie;Fueloep, Tamas, Jr.
通讯作者：
Fueloep, Tamas, Jr.
影响因子：
4.1
作者：
Araki-Sasaki, K;Ando, Y;Tanihara, H
通讯作者：
Tanihara, H
影响因子：
2.9
作者：
Arnusch, Christopher J.;Branderhorst, Hilbert;Pieters, Roland J.
通讯作者：
Pieters, Roland J.
DOI：
10.1016/b978-0-444-53488-0.00016-x
发表时间：
2014-01-01
期刊：
NEUROVIROLOGY
影响因子：
--
作者：
Hill, Joshua A.;Venna, Nagagopal
通讯作者：
Venna, Nagagopal
DOI：
10.3233/jad-142853
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Harris SA;Harris EA
通讯作者：
Harris EA