Chauhan Payal, Begum M Yasmin, Narapureddy Bayapa Reddy, Gupta Saurabh, Wadhwa Karan, Singh Govind, Kumawat Rohit, Sharma Naveen, Ballal Suhas, Jha Saurabh Kumar, Abomughaid Mosleh Mohammad, B Dheepak, Ojha Shreesh, Jha Niraj Kumar
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
Mol Neurobiol. 2025 May;62(5):5850-5874. doi: 10.1007/s12035-024-04535-4. Epub 2024 Dec 9.
Viruses pose a significant challenge and threat to human health, as demonstrated by the current COVID-19 pandemic. Neurodegeneration, particularly in the case of Alzheimer's disease (AD), is significantly influenced by viral infections. AD is a neurodegenerative disease that affects people of all ages and poses a significant threat to millions of individuals worldwide. The precise mechanism behind its development is not yet fully understood; however, the emergence and advancement of AD can be hastened by various environmental factors, such as bacterial and viral infections. There has been a longstanding suspicion that the herpes simplex virus-1 (HSV-1) may have a role to play in the development or advancement of AD. Reactivation of HSV-1 could potentially lead to damage to neurons, either by direct means or indirectly by triggering inflammation. This article provides an overview of the connection between HSV-1 infections and immune cells (astrocytes, microglia, and oligodendrocytes) in the progression of AD. It summarizes recent scientific research on how HSV-1 affects neurons, which could potentially shed light on the clinical features and treatment options for AD. In addition, the paper has explored the impact of HSV-1 on neurons and its role in various aspects of AD, such as Aβ secretion, tau hyperphosphorylation, metabolic dysregulation, oxidative damage, apoptosis, and autophagy. It is believed that the immune response triggered by HSV-1 reactivation plays a role in the development of neurodegeneration in AD. Despite the lack of a cure for AD, researchers have made significant efforts to study the clinical and pathological aspects of the disease, identify biomarkers, and gain insight into its underlying causes. The goal is to achieve early diagnosis and develop treatments that can modify the progression of the disease. The current article discusses the most promising therapy for combating the viral impacts, which provides additional evidence for the frequent reactivations of latent HSV-1 in the AD brain. However, further research is still required to establish the molecular and cellular mechanisms underlying the development of AD through the reactivation of HSV-1. This could potentially lead to new insights in drug development aimed at preventing HSV-1 reactivation and the subsequent development and progression of AD.
正如当前的新冠疫情所表明的那样，病毒对人类健康构成了重大挑战和威胁。神经退行性变，尤其是在阿尔茨海默病（AD）的情况下，会受到病毒感染的显著影响。AD是一种影响所有年龄段人群的神经退行性疾病，对全球数百万人构成重大威胁。其发病的确切机制尚未完全了解；然而，AD的出现和进展可能会因各种环境因素而加速，如细菌和病毒感染。长期以来，人们一直怀疑单纯疱疹病毒1型（HSV-1）可能在AD的发生或进展中起作用。HSV-1的重新激活可能会直接或通过引发炎症间接导致神经元损伤。本文概述了HSV-1感染与AD进展过程中免疫细胞（星形胶质细胞、小胶质细胞和少突胶质细胞）之间的联系。它总结了最近关于HSV-1如何影响神经元的科学研究，这可能有助于揭示AD的临床特征和治疗选择。此外，该论文探讨了HSV-1对神经元的影响及其在AD各个方面的作用，如Aβ分泌、tau过度磷酸化、代谢失调、氧化损伤、细胞凋亡和自噬。据信，HSV-1重新激活引发的免疫反应在AD神经退行性变的发展中起作用。尽管AD尚无治愈方法，但研究人员已做出重大努力来研究该疾病的临床和病理方面，识别生物标志物，并深入了解其潜在病因。目标是实现早期诊断并开发能够改变疾病进展的治疗方法。本文讨论了对抗病毒影响最有前景的疗法，这为AD大脑中潜伏HSV-1的频繁重新激活提供了额外证据。然而，仍需要进一步研究来确定通过HSV-1重新激活导致AD发展的分子和细胞机制。这可能会为旨在预防HSV-1重新激活以及随后AD的发展和进展的药物开发带来新的见解。
