Medical School, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
Neuroscience. 2023 Feb 21;512:110-132. doi: 10.1016/j.neuroscience.2022.12.007. Epub 2022 Dec 13.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the 2019 coronavirus disease (COVID-19), has affected more than 20 million people in Brazil and caused a global health emergency. This virus has the potential to affect various parts of the body and compromise metabolic functions. The virus-mediated neural inflammation of the nervous system is due to a storm of cytokines and oxidative stress, which are the clinical features of Alzheimer's disease (AD). This neurodegenerative disease is aggravated in cases involving SARS-CoV-2 and its inflammatory biomarkers, accelerating accumulation of β-amyloid peptide, hyperphosphorylation of tau protein, and production of reactive oxygen species, which lead to homeostasis imbalance. The cholinergic system, through neurons and the neurotransmitter acetylcholine (ACh), modulates various physiological pathways, such as the response to stress, sleep and wakefulness, sensory information, and the cognitive system. Patients with AD have low concentrations of ACh; hence, therapeutic methods are aimed at adjusting the ACh titers available to the body for maintaining functionality. Herein, we focused on acetylcholinesterase inhibitors, responsible for the degradation of ACh in the synaptic cleft, and muscarinic and nicotinic receptor agonists of the cholinergic system owing to the therapeutic potential of the cholinergic anti-inflammatory pathway in AD associated with SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是 2019 年冠状病毒病(COVID-19)的病原体,已在巴西影响了超过 2000 万人,并引发了全球卫生紧急情况。该病毒有可能影响身体的各个部位并损害代谢功能。病毒介导的神经系统神经炎症是由于细胞因子和氧化应激的风暴,这是阿尔茨海默病(AD)的临床特征。这种神经退行性疾病在涉及 SARS-CoV-2 及其炎症生物标志物的情况下会加重,加速β-淀粉样肽的积累、tau 蛋白的过度磷酸化和活性氧的产生,导致体内平衡失调。胆碱能系统通过神经元和神经递质乙酰胆碱(ACh)调节各种生理途径,如应激反应、睡眠和觉醒、感觉信息和认知系统。AD 患者的 ACh 浓度较低;因此,治疗方法旨在调节体内可用的 ACh 浓度以维持功能。在这里,我们重点介绍了乙酰胆碱酯酶抑制剂,它们负责在突触间隙中降解 ACh,以及胆碱能系统的毒蕈碱和烟碱受体激动剂,因为胆碱能抗炎途径在与 SARS-CoV-2 感染相关的 AD 中的治疗潜力。