Molecular docking and molecular dynamics simulations studies on the protective and pathogenic roles of the amyloid-β peptide between herpesvirus infection and Alzheimer's disease

Wang, He-Cheng; Zhang, Qiuxian; Zhao, Jing; Wei, Ning-Ning

doi:10.1016/j.jmgm.2022.108143

Cited by 8 publications

(5 citation statements)

References 62 publications

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“…Very recently, Wang et al [ 38 ] have provided in silico evidence that Aβ associates with the HSV-1-gD. Our experimental observations by FRET of intact viral particles indicates that Aβ binds to viral particles near the binding site of gB or directly to gB.…”

Section: Discussionmentioning

confidence: 55%

Interaction Mechanism Between the HSV-1 Glycoprotein B and the Antimicrobial Peptide Amyloid-β

Bourgade

Frost

Dupuis

et al. 2022

Journal of Alzheimer's Disease Reports

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Background: Unravelling the mystery of Alzheimer’s disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the amyloid-β peptide (Aβ) and the intracellular neurofibrillary tangles could occur within the brain without any cognitive pathology. Thus, these paradoxes suggest that something more fundamental is at play in the onset of the disease and other key and related pathomechanisms must be investigated. Objective: The present study follows our previous investigations on the infectious hypothesis, which posits that some pathogens are linked to late onset AD. Our studies also build upon the finding that Aβ is a powerful antimicrobial agent, produced by neurons in response to viral infection, capable of inhibiting pathogens as observed in in vitro experiments. Herein, we ask what are the molecular mechanisms in play when Aβ neutralizes infectious pathogens? Methods: To answer this question, we probed at nanoscale lengths with FRET (Förster Resonance Energy Transfer), the interaction between Aβ peptides and glycoprotein B (responsible of virus-cell binding) within the HSV-1 virion Results: The experiments show an energy transfer between Aβ peptides and glycoprotein B when membrane is intact. No energy transfer occurs after membrane disruption or treatment with blocking antibody. Conclusion: We concluded that Aβ insert into viral membrane, close to glycoprotein B, and participate in virus neutralization.

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Section: Discussionmentioning

confidence: 55%

Interaction Mechanism Between the HSV-1 Glycoprotein B and the Antimicrobial Peptide Amyloid-β

Bourgade

Frost

Dupuis

et al. 2022

Journal of Alzheimer's Disease Reports

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“…3 Aβ 42 stably binds to the envelope protein gD of HSV1, which interacts with the potential entry receptors of the host cell. 15 A neuroprotective effect of Aβ against herpesviruses was also confirmed in a 3D cell culture model using human neurons. 4 In neuronal cell culture experiments, HSV1 infection induced beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), resulting in increased amyloid turnover and elevated extracellular Aβ40 and Aβ42 levels in neuroblastoma cells and murine in vivo models.…”

Section: Current State Of Knowledgementioning

confidence: 76%

“…Aβ also displays an inhibitory activity against herpes simplex virus type 1 (HSV1) infection in neuronal cell culture 3 . Aβ 42 stably binds to the envelope protein gD of HSV1, which interacts with the potential entry receptors of the host cell 15 . A neuroprotective effect of Aβ against herpesviruses was also confirmed in a 3D cell culture model using human neurons 4 .…”

Section: Narrativementioning

confidence: 84%

Herpes simplex virus alters Alzheimer's disease biomarkers ‐ A hypothesis paper

Goldhardt

Freiberger

Dreyer

et al. 2022

Alzheimer's & Dementia

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Introduction: Human herpes simplex virus 1 (HSV1) is discussed to induce amyloidβ (Aβ) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. Aβ appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers.Methods: Aβ 42 /Aβ 40 ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A-). CSF-toserum anti-HSV1/2-IgG antibody indices (AI-IgG HSV1/2 ) and CMV (AI-IgG CMV ) were determined by enzyme-linked immunosorbent assay (ELISA).Results: Exclusively in HSV1-seropositive AD, pTau was positively and significantly predicted by AI-IgG HSV1/2 and negatively by the Aβ 42 /Aβ 40 ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI-IgG HSV1/2 and Aβ 42 /Aβ 40 ratio on pTau was found. Discussion:The results support the hypothesis that HSV infection contributes to AD.

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“…Bacteria and viruses, as well as several other infectious factors, are considered to be related to the pathogenesis of AD ( Lopatko Lindman et al, 2021 ; Figure 1 ). Notably, multiple excellent studies have steadily revealed the potential role of several viruses in AD pathology, such as herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), measles virus, adenoviruses, cytomegalovirus, poliovirus, hepatitis B virus, and influenza virus ( Wang et al, 2022 ). These works support the virus hypothesis and the potential of antiviral treatment to overcome AD.…”

Section: Introductionmentioning

confidence: 99%

“…Evidence that viral infection plays a role in AD has long been investigated. Some viruses that cause lifelong persistent infection are upregulated in the central nervous system (CNS) of AD patients and are associated with pathology ( Wang et al, 2022 ). Studies have found that approximately 25% of AIDS patients who did not receive combined antiretroviral therapy will develop neurological disorders associated with Aβ plaque deposition and tau protein aggregation ( Hategan et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The viral hypothesis in Alzheimer’s disease: SARS-CoV-2 on the cusp

Liu

Jiang

2023

Front. Aging Neurosci.

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Increasing evidence highlights that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has long-term effects on cognitive function, which may cause neurodegenerative diseases like Alzheimer’s disease (AD) in the future. We performed an analysis of a possible link between SARS-CoV-2 infection and AD risk and proposed several hypotheses for its possible mechanism, including systemic inflammation, neuroinflammation, vascular endothelial injury, direct viral infection, and abnormal amyloid precursor protein metabolism. The purpose of this review is to highlight the impact of infection with SASR-CoV-2 on the future risk of AD, to provide recommendations on medical strategies during the pandemic, and to propose strategies to address the risk of AD induced by SASR-CoV-2. We call for the establishment of a follow-up system for survivors to help researchers better understand the occurrence, natural history, and optimal management of SARS-CoV-2-related AD and prepare for the future.

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Molecular docking and molecular dynamics simulations studies on the protective and pathogenic roles of the amyloid-β peptide between herpesvirus infection and Alzheimer's disease

Cited by 8 publications

References 62 publications

Interaction Mechanism Between the HSV-1 Glycoprotein B and the Antimicrobial Peptide Amyloid-β

Interaction Mechanism Between the HSV-1 Glycoprotein B and the Antimicrobial Peptide Amyloid-β

Herpes simplex virus alters Alzheimer's disease biomarkers ‐ A hypothesis paper

The viral hypothesis in Alzheimer’s disease: SARS-CoV-2 on the cusp

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