Abstract:
Parkinson\'s disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD.
摘要:
帕金森病(PD)是一种普遍的神经退行性疾病,影响全球7-10百万人。PD的常见早期症状是嗅觉功能障碍(OD),超过90%的PD患者患有OD。最近的研究强调了SARS-CoV-2感染患者中OD的高发生率。这篇综述调查了OD在PD和COVID-19中的潜在趋同,特别关注神经炎症导致OD和神经系统事件的机制。从我们对嗅球的基本理解开始,我们从PD患者的临床病例和尸检报告中总结了OD的临床特征和嗅球的病理特征。然后,我们检查SARS-CoV-2诱导的嗅球神经病理学和OD,并强调SARS-CoV-2诱导的神经炎症级联反应可能导致PD表现。通过激活小胶质细胞和星形胶质细胞,以及促进α-突触核蛋白的聚集,SARS-CoV-2可能导致PD的发作或恶化。我们还讨论了NF-κB的可能贡献,NLRP3炎性体,和JAK/STAT,p38MAPK,TLR4、IL-6/JAK2/STAT3和cGAS-STING信号通路。尽管COVID-19患者的嗅觉功能障碍可能是可逆的,在PD患者中恢复OD具有挑战性。随着SARS-CoV-2新变种的出现和感染的复发,我们呼吁继续关注PD和SARS-CoV-2感染之间的交叉,尤其是从OD的角度来看。