Elechi Kelechi Wisdom, Oyepeju Nkem Ogundipe, Timothy Chibueze Ndubuisi, Elechi Ubalaeze Solomon, Franklin Chimaobi Kenechukwu
Integrated Biomedical Sciences, University of Texas Health San Antonio, San Antonio, TX, USA.
Stephen M. Ross School of Business, University of Michigan, Ann Arbor, MI, USA.
Neurosci Insights. 2025 May 29;20:26331055251342755. doi: 10.1177/26331055251342755. eCollection 2025.
SARS-CoV-2, the causative agent of COVID-19, has profound systemic effects, including significant impacts on the central nervous system (CNS). Emerging evidence suggests a potential link between SARS-CoV-2-induced neuroinflammation and the exacerbation or initiation of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This review explores the mechanisms by which SARS-CoV-2 may contribute to neurodegenerative processes. We first discuss the pathways of viral entry into the CNS, including transneuronal and hematogenous routes, leading to blood-brain barrier (BBB) dysfunction. Neuroinflammation, mediated by the activation of microglia and astrocytes and the release of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β, is highlighted as a critical factor exacerbating neuronal damage. Oxidative stress and vascular damage are further examined as complementary mechanisms promoting neurodegeneration. In addition, we review how SARS-CoV-2 infection influences proteinopathies by accelerating the aggregation of pathological proteins like alpha-synuclein, tau, and TDP-43, contributing to disease progression in PD, AD, and related disorders. Clinical studies reporting cognitive and motor dysfunctions in post-COVID-19 patients with pre-existing neurodegenerative diseases are also summarized. Finally, this review identifies knowledge gaps and emphasizes the need for further research to clarify the long-term neurological consequences of SARS-CoV-2 infection. Understanding these mechanisms is critical for developing targeted therapeutic strategies to mitigate the risk of neurodegeneration in vulnerable populations.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是冠状病毒病（COVID-19）的病原体，具有深远的全身影响，包括对中枢神经系统（CNS）的重大影响。新出现的证据表明，SARS-CoV-2诱导的神经炎症与阿尔茨海默病（AD）和帕金森病（PD）等神经退行性疾病的加重或发病之间存在潜在联系。本综述探讨了SARS-CoV-2可能导致神经退行性过程的机制。我们首先讨论病毒进入中枢神经系统的途径，包括跨神经元途径和血源性途径，这些途径会导致血脑屏障（BBB）功能障碍。由小胶质细胞和星形胶质细胞激活以及白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）等促炎细胞因子释放介导的神经炎症被认为是加剧神经元损伤的关键因素。氧化应激和血管损伤作为促进神经退行性变的补充机制将被进一步研究。此外，我们还综述了SARS-CoV-2感染如何通过加速α-突触核蛋白、tau蛋白和TDP-43等病理性蛋白质的聚集来影响蛋白质病，从而促进帕金森病、阿尔茨海默病及相关疾病的病情进展。还总结了关于患有神经退行性疾病的COVID-19康复患者出现认知和运动功能障碍的临床研究。最后，本综述指出了知识空白，并强调需要进一步研究以阐明SARS-CoV-2感染的长期神经学后果。了解这些机制对于制定有针对性的治疗策略以降低易感人群神经退行性变风险至关重要。
