Synaptotoxic Signaling by Amyloid Beta Oligomers in Alzheimer's Disease Through Prion Protein and mGluR5.
Synaptotoxic Signaling by Amyloid Beta Oligomers in Alzheimer's Disease Through Prion Protein and mGluR5.
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DOI：
10.1016/bs.apha.2017.09.007
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Strittmatter SM
中科院分区：
文献类型：
--
作者：
Brody AH;Strittmatter SM
阿尔茨海默病（AD）代表了即将到来的全球健康危机，然而AD病理生理学的复杂性迄今为止已经排除了成功减缓或停止AD进展的任何干预措施的开发。很明显，淀粉样蛋白-β（Aβ）肽的积累触发进行性突触丧失，导致AD症状。一旦由Aβ启动，炎症和tau病理就会使疾病进展变得复杂并加速。认识到Aβ肽呈现多种不同的状态以及可溶性寡聚物（Aβo）对突触损伤至关重要，这对于AD的分子理解至关重要。这一知识导致了特异性Aβo受体的鉴定，如细胞朊病毒蛋白（PrPC），介导突触毒性和神经元功能障碍。PrPC作为Aβo受体的鉴定阐明了Aβ o诱导的涉及mGluR 5、Fyn和Pyk 2的信号级联反应，其将Aβ和tau病理学联系起来。该通路为改善AD的疾病治疗提供了新的潜在治疗靶点。在这里，我们讨论的方法，其中几个假定的Aβo受体被确定。我们还提供了一个深入的研究已知的分子机制，认为介导Aβ o诱导的突触功能障碍，毒性和记忆功能障碍。
Alzheimer's disease (AD) represents an impending global health crisis, yet the complexity of AD pathophysiology has so far precluded the development of any interventions to successfully slow or halt AD progression. It is clear that accumulation of Amyloid-beta (Aβ) peptide triggers progressive synapse loss to cause AD symptoms. Once initiated by Aβ, disease progression is complicated and accelerated by inflammation and by tau pathology. The recognition that Aβ peptide assumes multiple distinct states and that soluble oligomeric species (Aβo) are critical for synaptic damage is central to molecular understanding of AD. This knowledge has led to the identification of specific Aβo receptors, such as cellular prion protein (PrPC), mediating synaptic toxicity and neuronal dysfunction. The identification of PrPC as an Aβo receptor has illuminated an Aβo-induced signaling cascade involving mGluR5, Fyn, and Pyk2 that links Aβ and tau pathologies. This pathway provides novel potential therapeutic targets for disease-modifying AD therapy. Here, we discuss the methods by which several putative Aβo receptors were identified. We also offer an in-depth examination of the known molecular mechanisms believed to mediate Aβo-induced synaptic dysfunction, toxicity, and memory dysfunction.
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DOI：
10.1097/nen.0b013e318217a118
发表时间：
2011-05
影响因子：
3.2
作者：
DaRocha-Souto B;Scotton TC;Coma M;Serrano-Pozo A;Hashimoto T;Serenó L;Rodríguez M;Sánchez B;Hyman BT;Gómez-Isla T
通讯作者：
Gómez-Isla T
DOI：
10.1523/jneurosci.4992-08.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bartos JA;Ulrich JD;Li H;Beazely MA;Chen Y;Macdonald JF;Hell JW
通讯作者：
Hell JW
影响因子：
3.6
作者：
Collins, Michaela;Bartelt, Rebekah R.;Houtman, Jon C. D.
通讯作者：
Houtman, Jon C. D.
影响因子：
82.9
作者：
Citron, M;Westaway, D;Selkoe, DJ
通讯作者：
Selkoe, DJ
影响因子：
11.1
作者：
Calella, Anna Maria;Farinelli, Melissa;Aguzzi, Adriano
通讯作者：
Aguzzi, Adriano