Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach

Talwar, Puneet; Gupta, Renu; Kushwaha, Suman; Agarwal, Rachna; Saso, Luciano; Kukreti, Shrikant; Kukreti, Ritushree

doi:10.2174/1570159x16666180419124508

Cited by 27 publications

(21 citation statements)

References 158 publications

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“…21 Furthermore, another study also found that HPV may also play a role in inducing oxidative and inflammatory response in Alzheimer's disease pathogenesis. 22 On the other hand, some researchers have found that the E6 and E7 genes of HPV 16 could protect astrocytes, 23,24 which have essential roles implicated in the pathogenesis of neurodegenerative disease, 25 from injury. Therefore, further studies are needed to investigate the association between HPV and the risk of dementia by using a nationwide database in Taiwan.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have shown that HPV may be detected in neurological diseases, for example, in the brains of patients with pediatric epilepsy and Rasmussen’s encephalitis . Furthermore, another study also found that HPV may also play a role in inducing oxidative and inflammatory response in Alzheimer’s disease pathogenesis . On the other hand, some researchers have found that the E6 and E7 genes of HPV 16 could protect astrocytes, which have essential roles implicated in the pathogenesis of neurodegenerative disease, from injury.…”

Section: Introductionmentioning

confidence: 99%

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Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan

Lin

Chien

Chung

et al. 2020

The Journal of Dermatology

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Genital warts are a common sexually transmitted disease caused by human papillomavirus (HPV) infections. The prevalence of dementia is 4-8% in those aged 65 years or older in Taiwanese community studies, with a high social and economic burden for patients, family caregivers, the community and society. Previous studies have shown that viral infections such as herpes simplex and herpes zoster were associated with dementia. This study aimed to investigate the association between dementia and HPV infections. A population-based cohort study using data from Taiwan's National Health Insurance Research Database was conducted. Fine and Grays's survival analysis was employed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between genital warts and dementia. From all of the potential participants aged 50 years or more, a total of 16 116 patients were enrolled, including 4029 genital warts-infected patients, with 12 087 sex-, age-and indexed date-matched controls (1:3). The cumulative incidences of dementia were 10.72 per 10 3 person-years and 6.43 per 10 3 person-years in the genital warts and control group, respectively. There were 475 dementia cases from the genital warts cohort during the follow-up period of 15 years. The adjusted HR for dementia was 1.485 (95% CI, 1.321-1.668; P < 0.001) for genital warts patients after adjusting for all of the covariates. Our study indicates that genital warts infection may increase the risk of dementia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan

Lin

Chien

Chung

et al. 2020

The Journal of Dermatology

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“…Out of the three APOEs, APOE □4 was the least potent and effective at preventing HIV-1 internalization 65 . To complete this model, it is highly likely that viral infection is accompanied by the activation of microglia cells causing inflammation including activation of TREM2 59,66,67 , corresponding to another AD susceptibility gene. Further research is necessary to underline this hypothetical model, which supports the benefit of an antiviral therapy for the treatment of AD as recently initiated 68 .…”

Section: Discussionmentioning

confidence: 99%

Amyloid precursor protein causes fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load

Marks

Heinen

Bachmann

et al. 2020

Preprint

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The amyloid precursor protein (APP) is a type I transmembrane protein with unknown physiological function but potential impact in neurodegeneration. The current study demonstrates that APP signals to the nucleus causing the generation of aggregates comprising its adapter protein FE65 and the tumour suppressor proteins p53 and PML. The PML nuclear body generation, known to be of relevance in virus defence and cell division, is induced and fusion occurs over time depending on APP signalling. We further show that the nuclear aggregates of APP C-terminal (APP-CT) fragments together with PML and FE65 are present in the aged human brain but not in cerebral organoids differentiated from iPS cells.Notably, human Alzheimer's disease brains reveal a highly significant loss of these nuclear aggregates in areas with high plaque load compared to plaque-free areas of the same individual. Based on these results we conclude that APP-CT signalling to the nucleus takes DPBS (Gibco) and fixed in 4 % paraformaldehyde in PBS. Cover glasses were mounted with the Shandon™ Immu-Mount™ solution (Thermo Scientific) on glass slides and dried overnight at RT. For immunofluorescence staining, HEK293T cells were seeded in 8-well-µslide-ibi Treat (ibidi ® , Martinsried, Germany) and transfected using calcium phosphate transfection after 24 h. Cells were fixed with Roti ® -Histofix 4 % (4 % phosphate buffered formaldehyde solution; Roth, Karlsruhe, DE) for 20 min at 37 °C, and permeabilized and blocked with 5 % normal goat serum (NGS) in 0.3 % (w/v) Triton X-100/PBS for 30 min at RT. The cells were incubated with primary antibodies diluted in 1 % BSA/0.3 % Triton X-100/DPBS (mouse anti-HA (BioLegend, 901501; 1:1000), mouse anti-myc (NEB/Cell Signaling, 2276; 1:1500) o/n at 4 °C. For the secondary antibody staining and the cell staining, goat-anti-mouse AF568 (Invitrogen, A11004, 1:1000) was used, together with HCS CellMask™ Deep Red Stain (ThermoFisher Scientific, H32721, 1:5000), Hoechst33342 (10 mg/ml in H2O, Applichem, A0741, 1:1000) in DPBS (1 % BSA, 0.3 % Triton) and incubated for 1 h at RT.Immunoprecipitation HEK 293T cells were seeded in 10 cm dishes and co-transfection was performed 24 h after seeding. Whole cell extracts were prepared 24 h after transfection by scraping the cells from the dish with a cell scraper, washing the cell pellet in ice-cold PBS, extracting with 1 ml interaction buffer (50 mM Tris pH 8, 150 mM NaCl, 5 mM EDTA, 0.5% NP40, 1 mM DTT, 1 mM PMSF, 1x complete protease inhibitor cocktail), followed by sonication (15 s at 95 % amplitude) using a Sonopuls mini20 device (Bandelin, Berlin, Germany). The lysates were centrifuged (15,000 g, 15 min, 4 °C) and the supernatant was transferred to a new reaction tube. Input samples of the lysates were stored separately. Immunoprecipitation (IP) was carried out with the µMACS isolation kits for tagged proteins from Miltenyi Biotec (Bergisch-Gladbach, Germany). The eluates, as well as input samples of the lysates were subjected to SDS-PAGE and immunoblotting.

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“…Degenerative diseases of the brain that have been linked to altered RAS include Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, other than stroke as mentioned above (86,98,99). Moreover, the dysregulation of the antiviral response is another factor that has been associated with neurodegenerative disease (100,101). It has been shown that products of certain genes may have potent antiviral activities, and may have deleterious effects when their expression is not appropriately regulated.…”

Section: Long Term Complication Of Covid 19 Invasion In the Brainmentioning

confidence: 99%

SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications

Khan

Sergi

2020

Front. Neurol.

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The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. Using the STRING bioinformatic tool and references through text mining tools associated to Coronaviruses, we identified SAMHD1 as the probable link to neurological symptoms. Paralleled to the response to influenza A virus and, specifically, respiratory syncytial virus, SARS-CoV-2 evokes a response that needs robust induction of a subclass of cytokines, including the Type I and, obviously, Type III interferons as well as a few chemokines. We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway. No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP. We suggest that SAMHD1 is the molecule that may be behind the mechanisms of the neurological complications associated with COVID-19.

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Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach

Cited by 27 publications

References 158 publications

Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan

Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan

Amyloid precursor protein causes fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load

SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications

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