Cognitive impact of COVID-19: looking beyond the short term

Alzheimer s Research & Therapy, Год журнала: 2020, Номер 12(1)

Опубликована: Дек. 1, 2020

COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It unclear how much the ischaemic damage mediated by direct or inflammatory effects virus on CNS vasculature secondary extracranial cardiorespiratory disease. Limited data suggest that causative SARS-CoV-2 may enter via nasal mucosa olfactory fibres, haematogenous spread, capable infecting endothelial cells, pericytes probably neurons. Extracranially, targets cells pericytes, causing cell dysfunction, vascular leakage immune activation, sometimes leading disseminated intravascular coagulation. remains be confirmed whether cerebral are similarly targeted. Several aspects likely impact cognition. Cerebral white matter particularly vulnerable also critically important for cognitive function. There accumulating hypoperfusion accelerates amyloid-β (Aβ) accumulation linked tau TDP-43 pathology, inducing phosphorylation α-synuclein at serine-129, ischaemia increase risk development Lewy body Current therapies understandably focused supporting function, preventing thrombosis reducing activation. Since angiotensin-converting enzyme (ACE)-2 receptor SARS-CoV-2, ACE inhibitors angiotensin blockers predicted ACE-2 expression, it was initially feared their use might exacerbate COVID-19. Recent meta-analyses have instead suggested these medications protective. This perhaps because entry deplete ACE-2, tipping balance towards II-ACE-1-mediated classical RAS activation: exacerbating promoting inflammation. relevant APOE ε4 individuals, who seem increased COVID-19, lowest activity. leave an unexpected legacy long-term neurological complications significant number survivors. Cognitive follow-up will important, especially develop cerebrovascular during acute illness.

Язык: Английский

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SARS-CoV-2 Infectivity and Neurological Targets in the Brain

Cellular and Molecular Neurobiology, Год журнала: 2020, Номер 42(1), С. 217 - 224

Опубликована: Авг. 25, 2020

The gateway for invasion by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human host cells is via angiotensin-converting enzyme (ACE2) transmembrane receptor expressed in multiple immune and nonimmune cell types. SARS-CoV-2, that causes disease 2019 (COVID-19; CoV-19) has unusual capacity to attack many different types of simultaneously clathrin- caveolae-independent endocytic pathways, becoming injurious diverse cells, tissues organ systems exploiting any weakness host. elicitation this multipronged explains part severity extensive variety signs symptoms observed CoV-19 patients. To further our understanding mechanism pathways SARS-CoV-2 infection susceptibility specific cell- tissue-types communication we analyzed ACE2 expression 85 including 21 brain regions, 7 fetal 8 controls. Besides strong respiratory, digestive, renal-excretory reproductive high was also found amygdala, cerebral cortex brainstem. highest level pons medulla oblongata brainstem, containing medullary centers brain, may explain patients distress.

Язык: Английский

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MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(12), С. 4471 - 4471

Опубликована: Июнь 23, 2020

The signaling pathway of the microtubule-associated protein kinase or extracellular regulated (MAPK/ERK) is a common mechanism information transduction from stimuli to intracellular space. leads changes in ongoing metabolic pathways and modification gene expression patterns. In central nervous system, ERK expressed ubiquitously, both temporally spatially. As for temporal ubiquity, this system participates three key moments: (i) Embryonic development; (ii) early postnatal period; iii) adulthood. During embryonic development, partly responsible patterning segmentation encephalic vesicle through FGF8-ERK pathway. addition, during period, directs neurogenesis migration final fate neural progenitors. maturation process dendritic trees synaptogenesis. adulthood, social emotional behavior memory processes, including long-term potentiation. Alterations mechanisms related are associated with different pathological outcomes. Genetic alterations any component result pathologies crest derivatives mental dysfunctions autism spectrum disorders. MAP-ERK element neuroinflammatory triggered by glial cells development neurodegenerative diseases, such as Parkinson's Alzheimer's disease, Huntington's amyotrophic lateral sclerosis, well prionic diseases. MAPK/ERK activation depends on stage (mature senescence), type cellular which activated, anatomic structure. However, extensive gaps exist regards targets phosphorylated many these processes.

Язык: Английский

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Angiotensin-converting enzyme 2—at the heart of the COVID-19 pandemic

Cell, Год журнала: 2023, Номер 186(5), С. 906 - 922

Опубликована: Фев. 2, 2023

ACE2 is the indispensable entry receptor for SARS-CoV and SARS-CoV-2. Because of COVID-19 pandemic, it has become one most therapeutically targeted human molecules in biomedicine. serves two fundamental physiological roles: as an enzyme, alters peptide cascade balance; a chaperone, controls intestinal amino acid uptake. ACE2's tissue distribution, affected by co-morbidities sex, explains broad tropism coronaviruses clinical manifestations SARS COVID-19. ACE2-based therapeutics provide universal strategy to prevent treat SARS-CoV-2 infections, applicable all variants other emerging zoonotic exploiting their cellular receptor.

Язык: Английский

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SARS-CoV-2: is there neuroinvasion?

Fluids and Barriers of the CNS, Год журнала: 2021, Номер 18(1)

Опубликована: Июль 14, 2021

Abstract Background SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes hypertension. These conditions are associated vascular dysfunction, the CoV disease 2019 (COVID-19) complications include multiorgan failure neurological problems. While main route entry into body inhalation, this virus has been found many tissues, including choroid plexus meningeal vessels, neurons CSF. Main We reviewed SARS-CoV-2/COVID-19, ACE2 distribution beneficial effects, CNS barriers, possible mechanisms by which enters brain, outlined (obesity, hypertension diabetes), COVID-19 manifestation aging cerebrovascualture. The overall aim provide general reader breadth information on type wide its receptor so better understand significance uniqueness pre-existing medical that affect brain. issue there no sound evidence for large flux SARS-CoV-2 at present, compared invasion inhalation pathways. Conclusions detected brains from severely infected patients, it unclear how gets there. There brain significantly contribute outcomes once system invaded virus. consensus, based normal infection presence olfactory mucosa Studies needed demonstrate replication parenchyma neuroinvasion. It manifestations consequence mainly cardio-respiratory failure. Understanding potential neuroinvasion pathways could help define COVID-19.

Язык: Английский

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Blood-Brain Barrier Crossing Renin-Angiotensin Drugs and Cognition in the Elderly: A Meta-Analysis

Hypertension, Год журнала: 2021, Номер 78(3), С. 629 - 643

Опубликована: Июнь 21, 2021

Hypertension is an established risk factor for cognitive decline and dementia in older adults, highlighting the potential importance of antihypertensive treatments prevention efforts. Work surrounding has suggested possible salutary effects on cognition neuropathology. Several studies have specifically highlighted renin-angiotensin system drugs, including AT1-receptor blockers angiotensin-converting-enzyme inhibitors, as potentially benefiting later life. A small number further drugs that cross blood-brain barrier may be linked to lower compared their nonpenetrant counterparts. The present meta-analysis sought evaluate benefits crossing relative We harmonized longitudinal participant data from 14 cohorts 6 countries (Australia, Canada, Germany, Ireland, Japan, United States), a total 12 849 individuals at baseline, assessed within medications used by cognitively normal participants. analyzed 7 domains (attention, executive function, language, verbal memory learning, recall, mental status, processing speed) using ANCOVA (adjusted age, sex, education) meta-analyses. Older adults taking barrier-crossing exhibited better recall over up 3 years follow-up, those medications, despite relatively higher vascular burden. Conversely, nonblood-brain barrier-penetrant showed attention same follow-up period, although burden partially explain this result. Findings suggest links between less decline.

Язык: Английский

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Targeting brain Renin-Angiotensin System for the prevention and treatment of Alzheimer’s disease: Past, present and future

Ageing Research Reviews, Год журнала: 2022, Номер 77, С. 101612 - 101612

Опубликована: Март 26, 2022

Alzheimer's disease (AD) is a well-known neurodegenerative characterized by the presence of two main hallmarks – Tau hyperphosphorylation and Aβ deposits. Notwithstanding, in last few years scientific evidence about drivers AD have been changing nowadays age-related vascular alterations several cardiovascular risk factors shown to trigger development AD. In this context, drugs targeting Renin Angiotensin System (RAS), commonly used for treatment hypertension, are evidencing high potential delay due their action on brain RAS. Indeed, ACE 1/Ang II/AT1R axis believed be upregulated responsible deleterious effects such as increased oxidative stress, neuroinflammation, blood-brain barrier (BBB) hyperpermeability, astrocytes dysfunction decrease cerebral blood flow. contrast, alternative II/AT2R; 2/Ang (1−7)/MasR; Ang IV/ AT4R(IRAP) seems counterbalance principal exert beneficial memory cognition. Accordingly, retrospective studies demonstrate reduced developing among people taking RAS medication well vitro vivo pre-clinical it herein critically reviewed. review, we first revise, at glance, pathophysiology focused its classic hallmarks. Secondly, an overview impact also provided, four essential axes II/AT1R. Finally, therapeutic available AD, namely angiotensin II receptor blockers (ARBs) converting enzyme inhibitors (ACEIs), highlighted data supporting hope will presented, from clinical studies.

Язык: Английский

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The COVID-19 pandemic and Alzheimer’s disease: mutual risks and mechanisms

Translational Neurodegeneration, Год журнала: 2022, Номер 11(1)

Опубликована: Сен. 11, 2022

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment the spike protein to angiotensin-converting enzyme (ACE2) receptor expressed on cell membranes. Patients Alzheimer's (AD) more susceptible infection prone outcomes. Recent studies have revealed some common risk factors for AD COVID-19. An understanding association between potential related mechanisms may lead development novel approaches treating both diseases. In present review, we first summarize central nervous system (CNS) then discuss associations shared key AD, focus ACE2 receptor, apolipoprotein E (APOE) genotype, age, neuroinflammation.

Язык: Английский

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Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know?

International Journal of Environmental Research and Public Health, Год журнала: 2023, Номер 20(3), С. 2146 - 2146

Опубликована: Янв. 25, 2023

Alzheimer’s disease (AD) is a life-changing condition whose etiology explained by several hypotheses. Recently, new virus contributed to the evidence of viral involvement in AD: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 disease. AD was found be one most common comorbidities, and it increase mortality from this as well. Moreover, patients were observed present with distinct clinical features COVID-19, delirium being prevalent group. The SARS-CoV-2 enters host cells through angiotensin-converting enzyme (ACE2) receptor. ACE2 overexpressed brains AD, thus increases invasion. Furthermore, inhibition receptor may also decrease brain-derived neurotrophic factor (BDNF), contributing neurodegeneration. ApoE ε4 allele, risk facilitate entry into cells. neuroinflammation oxidative stress existing enhance inflammatory response associated COVID-19. pandemic social distancing measures negatively affected mental health, cognitive function, neuro-psychiatric symptoms patients. This review comprehensively covers links between disease, including presentation, molecular mechanisms, effects distancing.

Язык: Английский

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The classical and non-classical axes of renin-angiotensin system in Parkinson disease: The bright and dark side of the moon

Ageing Research Reviews, Год журнала: 2024, Номер 94, С. 102200 - 102200

Опубликована: Янв. 17, 2024

Язык: Английский

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