The roles of the kynurenine pathway in COVID-19 neuropathogenesis.

IF 5.4 2区医学 Q1 INFECTIOUS DISEASES

Infection Pub Date : 2024-10-01 Epub Date: 2024-05-27 DOI:10.1007/s15010-024-02293-y

Mona Dehhaghi, Mostafa Heydari, Hamed Kazemi Shariat Panahi, Sharon R Lewin, Benjamin Heng, Bruce J Brew, Gilles J Guillemin

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引用次数: 0

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.

Abstract Image

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犬尿氨酸途径在 COVID-19 神经发病机制中的作用

严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）是传染性极强的呼吸道疾病科罗娜病毒病 2019（COVID-19）的病原体，它可能导致各种神经和心理疾病，这些疾病可能是急性的，持续数天到数周或数月，也可能更长。后者被称为长COVID或最近的COVID急性后遗症（PASC）。在急性 COVID-19 感染期间，一些患者会出现强烈的炎症反应，即细胞因子风暴。干扰素-γ（IFN-γ）、干扰素-β（IFN-β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平尤其升高。众所周知，这些细胞因子会激活吲哚胺 2,3-二氧化酶 1（IDO-1），通过犬尿氨酸途径（KP）催化色氨酸（Trp）分解代谢的第一步，从而产生多种神经毒性和免疫抑制性代谢物。已有数据显示，KP 代谢物在急性期和 PASC 中都会升高，尤其是在认知障碍方面。因此，在 SARS-CoV-2 发病机制中，KP 的参与很可能非常重要，尤其是在神经系统方面。

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来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.