Apolipoprotein E and viral infection: Risks and Mechanisms

Molecular Therapy — Nucleic Acids, Год журнала: 2023, Номер 33, С. 529 - 542

Опубликована: Июль 29, 2023

Apolipoprotein E (ApoE) is a multifunctional protein critical for lipid metabolism and cholesterol homeostasis. In addition to being well known genetic determinant of both neurodegenerative cardiovascular diseases, ApoE frequently involved in various viral infection-related diseases. Human functionally polymorphic with three isoforms, namely, ApoE2, ApoE3, ApoE4, markedly altered structures functions. ApoE4 associated increased susceptibility infection herpes simplex virus type-1 HIV. Conversely, protects against hepatitis C B infection. With the outbreak coronavirus disease 2019, has been shown determine incidence progression severe acute respiratory syndrome 2 These findings clearly indicate role Furthermore, polymorphism or even opposite effects these processes, which are partly related structural features that distinguish different statuses. current review, we summarize emerging relationship between infection, discuss potential mechanisms, identify future directions may help advance our understanding link

Язык: Английский

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Molecular cross-talk between long COVID-19 and Alzheimer’s disease

GeroScience, Год журнала: 2024, Номер 46(3), С. 2885 - 2899

Опубликована: Фев. 23, 2024

Abstract The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some its symptoms affect nervous system and resemble Alzheimer’s disease (AD)—a neurodegenerative caused by accumulation amyloid beta hyperphosphorylation tau proteins. Multiple studies have found dependence between these two conditions. Patients with greater risk SARS-CoV-2 infection due to increased levels angiotensin-converting enzyme 2 (ACE2), itself promotes generation which enhances AD. Also, molecular pathways are alike—misregulations in folate-mediated one-carbon metabolism, deficit Cq10, disease-associated microglia. Medical imaging both diseases shows decrease volume gray matter, global brain size reduction, hypometabolism parahippocampal gyrus, thalamus, cingulate cortex. In some studies, similar approach applied medication can be seen, including use amino adamantanes phenolic compounds rosemary. significance connections their possible application medical practice still needs further study but there possibility that they will help better understand COVID.

Язык: Английский

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The Apoprotein E4 isotype does not affect the severity of COVID-19 infection and other flu-like syndromes

Journal of Medical Microbiology, Год журнала: 2025, Номер 74(1)

Опубликована: Янв. 22, 2025

Impact of e4 allele on flu-like syndromes The ɛ4 has no influence syndrome, including COVID-19. COVID-19 severity was associated with BMI, male sex, comorbidities and IL-4 levels.

Язык: Английский

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Genetic mutations associated with severe respiratory diseases

South of Russia ecology development, Год журнала: 2025, Номер 19(4), С. 28 - 40

Опубликована: Янв. 21, 2025

Aim. To analyze existing data on the impact of mutations in human genome pathogenesis respiratory viral infections and to discuss their relevance clinical practice. The primary objectives include describing mechanisms genetic mutations, reviewing examples genes that affect susceptibility disease severity evaluating prospects for testing personalized medicine.Research factors influencing demonstrates significant progression outcomes. For instance, IFITM3 gene, which plays a crucial role limiting influenza virus replication, along with its rs12252‐C polymorphism, is linked severe cases influenza. Similarly, TLR7 gene are associated manifestations COVID‐19, particularly males. These findings underscore importance identify individuals at heightened risk emphasize potential medicine enhance patient Additionally, it essential consider interplay between environmental as well social determinants health.This review examines influence progression. It can significantly course these infections. integrating into practice efficiency diagnosis, prognosis treatment emphasized.

Язык: Английский

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COVID-19 and Alzheimer’s Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future

Cells, Год журнала: 2023, Номер 12(22), С. 2601 - 2601

Опубликована: Ноя. 10, 2023

A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia has had tremendous impact on global economy and health since three years after its outbreak in December 2019- Alzheimer’s Disease (AD), leading cause dementia among human beings, reaching 139 million by year 2050. Even though COVID-19 is primary respiratory disease, causative agent, so-called Severe Acute Respiratory Syndrome 2 (SARS-CoV-2), also endowed with high neuro-invasive potential (Neurocovid). The neurological complications COVID-19, resulting from direct viral entry into Central Nervous System (CNS) and/or indirect systemic inflammation dysregulated activation immune response, encompass memory decline anosmia which are typically associated AD symptomatology. In addition, patients diagnosed more vulnerable to SARS-CoV-2 infection inclined clinical outcomes. present review, we better elucidate intimate connection summarizing involved risk factors/targets underlying biological mechanisms shared these two disorders particular focus Angiotensin-Converting Enzyme (ACE2) receptor, APOlipoprotein E (APOE), aging, neuroinflammation cellular pathways Amyloid Precursor Protein (APP)/Amyloid beta (Aβ) tau neuropathologies. Finally, involvement ophthalmological manifestations, including vitreo-retinal abnormalities visual deficits, both discussed. Understanding common physiopathological aspects linking will pave way novel management diagnostic/therapeutic approaches cope them post-pandemic future.

Язык: Английский

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Blood ACE2 protein level correlates with COVID-19 severity

Опубликована: Июнь 5, 2023

ACE2 impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects main risk factors and comorbidities, we involved post-COVID-19 patients Ternopil region (Ukraine). Recruitment period was July 2020 to December 2021. Medical records, treatment modalities outcomes were recorded analyzed. Serum human protein measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis performed SPSS21.0 software (SPSS Inc., Chicago, IL, The level serum significantly higher (p < 0.001) mild symptoms compared more severe course disease, inversely had changed from 1 90 days after recovery. In COVID-19, decreased over time, while among critical patients, it increased by 34.1percent. Such results could be explained shedding tissues into circulation. Loss membrane-bound form enzyme decreases virus entry cells. Our studies did not identify any sex-related levels correlation. most common comorbidities hypertension, cardiovascular diseases, respiratory diseases diabetes mellitus. All except contribute disease correlate blood level.

Язык: Английский

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Spotlight on contributory role of host immunogenetic profiling in SARS-CoV-2 infection: Susceptibility, severity, mortality, and vaccine effectiveness

Life Sciences, Год журнала: 2023, Номер 328, С. 121907 - 121907

Опубликована: Июнь 30, 2023

Язык: Английский

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Blood ACE2 Protein Level Correlates with COVID-19 Severity

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13957 - 13957

Опубликована: Сен. 11, 2023

ACE2's impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects main risk factors and comorbidities, we involved post-COVID-19 patients Ternopil region (Ukraine). The recruitment period was from July 2020 to December 2021. Medical records, treatment modalities, outcomes were recorded analyzed. serum human ACE2 protein measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis performed SPSS21.0 software (SPSS Inc., Chicago, IL, level significantly higher (p < 0.001) mild symptoms compared a more severe course disease, inversely had changed 1 90 days after recovery. In COVID-19, levels decreased over time, while among critical patients, it increased by 34.1 percent. Such results could be explained shedding tissues into circulation. Loss membrane-bound form enzyme decreases virus' entry cells. Our studies did not identify sex-related correlation. most common comorbidities hypertension, cardiovascular diseases, respiratory diabetes mellitus. All abovementioned except diseases contribute disease correlate blood levels.

Язык: Английский

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Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes

Open Biology, Год журнала: 2024, Номер 14(6)

Опубликована: Июнь 1, 2024

Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different via vascular system. We studied impact of apolipoprotein E (APOE) genotype inflammation on infectivity pseudo-typed severe acute syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse human cultured endothelial cells pericytes. Possessing APOE4 allele or having existing systemic enhance severity COVID-19. Using targeted replacement APOE3 mice induced bacterial lipopolysaccharide (LPS), we investigated infection SARS-CoV-2. Here, show that higher murine cerebrovascular pericytes compared cultures expressing APOE4. Furthermore, increasing inflammatory state prior incubation with LPS increased into cells. Our findings provide insights mechanisms underlying infection, highlighting how risk factors such as may exacerbate augmenting virus’s ability infect

Язык: Английский

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APOE2 protects against Aβ pathology by improving neuronal mitochondrial function through ERRα signaling

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Июнь 12, 2024

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative and apolipoprotein E (APOE) genotypes (APOE2, APOE3, APOE4) show different AD susceptibility. Previous studies indicated that individuals carrying the APOE2 allele reduce risk of developing AD, which may be attributed to potential neuroprotective role APOE2. However, mechanisms underlying protective effects still unclear. Methods We analyzed single-nucleus RNA sequencing bulk data APOE3 carriers from Religious Orders Study Memory Aging Project (ROSMAP) cohort. validated findings in SH-SY5Y cells model mice by evaluating mitochondrial functions cognitive behaviors respectively. Results The pathway analysis six major cell types revealed strong association between cellular stress energy metabolism, particularly excitatory inhibitory neurons, was found more pronounced presence beta-amyloid (Aβ). Moreover, overexpression alleviates Aβ1-42-induced dysfunction reduces generation reactive oxygen species cells. These due ApoE2 interacting with estrogen-related receptor alpha (ERRα). ERRα plasmids or activation agonist also similar Aβ1-42-stimulated Additionally, treatment improve performance Aβ injected both Y maze novel object recognition tests. increased PSD95 expression cortex agonist-treated-AD mice. Conclusions appears enhance neural function via signaling, effect treat AD.

Язык: Английский

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