COVID-19 患者大脑中的类阿尔茨海默病信号。
Alzheimer's-like signaling in brains of COVID-19 patients.
机构信息
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
出版信息
Alzheimers Dement. 2022 May;18(5):955-965. doi: 10.1002/alz.12558. Epub 2022 Feb 3.
INTRODUCTION
The mechanisms that lead to cognitive impairment associated with COVID-19 are not well understood.
METHODS
Brain lysates from control and COVID-19 patients were analyzed for oxidative stress and inflammatory signaling pathway markers, and measurements of Alzheimer's disease (AD)-linked signaling biochemistry. Post-translational modifications of the ryanodine receptor/calcium (Ca2 ) release channels (RyR) on the endoplasmic reticuli (ER), known to be linked to AD, were also measured by co-immunoprecipitation/immunoblotting of the brain lysates.
RESULTS
We provide evidence linking SARS-CoV-2 infection to activation of TGF-β signaling and oxidative overload. The neuropathological pathways causing tau hyperphosphorylation typically associated with AD were also shown to be activated in COVID-19 patients. RyR2 in COVID-19 brains demonstrated a "leaky" phenotype, which can promote cognitive and behavioral defects.
DISCUSSION
COVID-19 neuropathology includes AD-like features and leaky RyR2 channels could be a therapeutic target for amelioration of some cognitive defects associated with SARS-CoV-2 infection and long COVID.
简介
导致与 COVID-19 相关认知障碍的机制尚不清楚。
方法
分析对照和 COVID-19 患者的脑裂解物中的氧化应激和炎症信号通路标志物，以及阿尔茨海默病 (AD) 相关信号生物化学的测量值。还通过共免疫沉淀/免疫印迹脑裂解物测量内质网 (ER) 上的兰尼碱受体/钙 (Ca2+) 释放通道 (RyR) 的翻译后修饰，已知与 AD 相关。
结果
我们提供了将 SARS-CoV-2 感染与 TGF-β 信号和氧化过载激活联系起来的证据。与 AD 通常相关的tau 过度磷酸化引起的神经病理学途径也在 COVID-19 患者中被证明被激活。COVID-19 大脑中的 RyR2 表现出“渗漏”表型，这可能会促进认知和行为缺陷。
讨论
COVID-19 神经病理学包括 AD 样特征，渗漏的 RyR2 通道可能是改善与 SARS-CoV-2 感染和长 COVID 相关的一些认知缺陷的治疗靶点。
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