The Potential Role of Herpes Simplex Virus Type 1 and Neuroinflammation in the Pathogenesis of Alzheimer's Disease.
The Potential Role of Herpes Simplex Virus Type 1 and Neuroinflammation in the Pathogenesis of Alzheimer's Disease.
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DOI：
10.3389/fneur.2021.658695
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发表时间：
2021
影响因子：
3.4
通讯作者：
Enquist LW
中科院分区：
文献类型：
--
作者：
Laval K;Enquist LW
阿尔茨海默病(AD)是一种影响全球约5000万人的神经退行性疾病。到目前为止，还没有治愈方法，目前的治疗方法在延缓疾病进展方面也没有效果。因此，迫切需要更好地了解AD的发病机制，并重新考虑可能的治疗方法。单纯疱疹病毒1型(HSV1)最近因其在散发性AD中的潜在作用而受到越来越多的关注。该病毒是一种普遍存在的人类病原体，它感染粘膜上皮细胞，并入侵宿主的周围神经系统(PNS)，建立一种可激活的潜伏感染。一旦重新激活，HSV1就会扩散回上皮细胞，并引发新的感染，导致上皮损伤。偶尔，病毒会在重新激活后从PNS传播到大脑。在这篇综述中，我们讨论了目前关于AD发病机制的工作，并总结了支持HSV1在AD感染假说中的潜在作用的研究结果。我们还重点介绍了关于神经炎性反应的最新发现，神经炎性反应被认为是AD的主要驱动力，始于疾病的早期。还讨论了研究AD神经炎症的相关啮齿动物模型和新的治疗方法。在整个综述中，我们集中在HSV1发病机制的几个方面，包括它作为PNS的主要入侵者，在AD的病因学中应该被考虑。我们还指出了一些相互矛盾的数据和剩余的知识差距，需要进一步的研究才能最终完全理解人类阿尔茨海默病的病因。
Alzheimer's disease (AD) is a neurodegenerative disease affecting ~50 million people worldwide. To date, there is no cure and current therapies have not been effective in delaying disease progression. Therefore, there is an urgent need for better understanding of the pathogenesis of AD and to rethink possible therapies. Herpes simplex virus type 1 (HSV1) has recently received growing attention for its potential role in sporadic AD. The virus is a ubiquitous human pathogen that infects mucosal epithelia and invades the peripheral nervous system (PNS) of its host to establish a reactivable, latent infection. Upon reactivation, HSV1 spreads back to the epithelium and initiates a new infection, causing epithelial lesions. Occasionally, the virus spreads from the PNS to the brain after reactivation. In this review, we discuss current work on the pathogenesis of AD and summarize research results that support a potential role for HSV1 in the infectious hypothesis of AD. We also highlight recent findings on the neuroinflammatory response, which has been proposed to be the main driving force of AD, starting early in the course of the disease. Relevant rodent models to study neuroinflammation in AD and novel therapeutic approaches are also discussed. Throughout this review, we focus on several aspects of HSV1 pathogenesis, including its primary role as an invader of the PNS, that should be considered in the etiology of AD. We also point out some of the contradictory data and remaining knowledge gaps that require further research to finally fully understand the cause of AD in humans.
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影响因子：
12.7
作者：
Arbel-Ornath M;Hudry E;Eikermann-Haerter K;Hou S;Gregory JL;Zhao L;Betensky RA;Frosch MP;Greenberg SM;Bacskai BJ
通讯作者：
Bacskai BJ
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
13.3
作者：
Cho, Mi-Hyang;Cho, Kwangmin;Yoon, Seung-Yong
通讯作者：
Yoon, Seung-Yong
影响因子：
4
作者：
Bakker EN;Bacskai BJ;Arbel-Ornath M;Aldea R;Bedussi B;Morris AW;Weller RO;Carare RO
通讯作者：
Carare RO