Role of Microbes in the Development of Alzheimer's Disease: State of the Art - An International Symposium Presented at the 2017 IAGG Congress in San Francisco.
Role of Microbes in the Development of Alzheimer's Disease: State of the Art - An International Symposium Presented at the 2017 IAGG Congress in San Francisco.
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DOI：
10.3389/fgene.2018.00362
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发表时间：
2018
影响因子：
3.7
通讯作者：
Barron AE
中科院分区：
文献类型：
--
作者：
Fülöp T;Itzhaki RF;Balin BJ;Miklossy J;Barron AE
本文回顾了2017年7月在旧金山弗朗西斯科举行的国际老年学和老年医学协会（IAGG）大会特别研讨会上提出的研究结果和想法。五名研究人员介绍了他们与感染和阿尔茨海默病（AD）有关的结果。Itzhaki教授介绍了她关于病毒，特别是HSV-1在AD发病机制中的作用的工作。她坚持认为，尽管大多数人确实患有HSV-1感染，无论是潜伏的还是活跃的，但疱疹感染的各个方面都可以在AD的发病机制中发挥作用，这是基于AD大脑和感染细胞培养的广泛实验证据。Miklossy博士介绍了与AD相关的细菌感染的高患病率的研究，特别是螺旋体感染，世纪以来，螺旋体感染被认为是痴呆症的重要原因（例如，梅毒）。她展示了螺旋体如何驱动老年斑的形成，而老年斑实际上是生物膜。Balin教授随后描述了肺炎衣原体细菌对脑组织感染的影响，其可能在其传播中使用先天免疫系统，以及其引发AD特征性组织损伤。Fülöp教授描述了AD相关β淀粉样蛋白（Aβ）肽作为抗细菌、抗真菌和抗病毒先天免疫效应物的作用，该效应物是在对攻击大脑的微生物的反应中产生的。巴伦教授提出了一个新的假设，根据她的实验，AD相关Aβ与另一种普遍存在的重要的人类先天免疫效应物cathelicidin肽LL-37之间存在强序列特异性结合。鉴于这种结合，LL-37在脑中的表达将通过形成无毒的可溶性Aβ/LL-37复合物来减少Aβ沉积。因此，LL-37的慢性低表达可能是同时允许脑组织慢性感染和允许Aβ病理性蓄积的因素。这是第一次此类研讨会开辟了研究AD发病机制的范式转变的道路，从“淀粉样蛋白级联假说”，到目前为止还相当不成功，到一个新的“感染假说”，或者更广泛地说，“先天免疫系统失调假说”，这可能会很好地允许并导致发现AD患者的新治疗方法。
This article reviews research results and ideas presented at a special symposium at the International Association of Gerontology and Geriatrics (IAGG) Congress held in July 2017 in San Francisco. Five researchers presented their results related to infection and Alzheimer’s disease (AD). Prof. Itzhaki presented her work on the role of viruses, specifically HSV-1, in the pathogenesis of AD. She maintains that although it is true that most people harbor HSV-1 infection, either latent or active, nonetheless aspects of herpes infection can play a role in the pathogenesis of AD, based on extensive experimental evidence from AD brains and infected cell cultures. Dr. Miklossy presented research on the high prevalence of bacterial infections that correlate with AD, specifically spirochete infections, which have been known for a century to be a significant cause of dementia (e.g., in syphilis). She demonstrated how spirochetes drive senile plaque formation, which are in fact biofilms. Prof. Balin then described the involvement of brain tissue infection by the Chlamydia pneumoniae bacterium, with its potential to use the innate immune system in its spread, and its initiation of tissue damage characteristic of AD. Prof. Fülöp described the role of AD-associated amyloid beta (Aβ) peptide as an antibacterial, antifungal and antiviral innate immune effector produced in reaction to microorganisms that attack the brain. Prof. Barron put forward the novel hypothesis that, according to her experiments, there is strong sequence-specific binding between the AD-associated Aβ and another ubiquitous and important human innate immune effector, the cathelicidin peptide LL-37. Given this binding, LL-37 expression in the brain will decrease Aβ deposition via formation of non-toxic, soluble Aβ/LL-37 complexes. Therefore, a chronic underexpression of LL-37 could be the factor that simultaneously permits chronic infections in brain tissue and allows for pathological accumulation of Aβ. This first-of-its-kind symposium opened the way for a paradigm shift in studying the pathogenesis of AD, from the “amyloid cascade hypothesis,” which so far has been quite unsuccessful, to a new “infection hypothesis,” or perhaps more broadly, “innate immune system dysregulation hypothesis,” which may well permit and lead to the discovery of new treatments for AD patients.
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影响因子：
4
作者：
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通讯作者：
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影响因子：
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