Neuroinflammation in Alzheimer’s Disease

Biomedicines, Год журнала: 2021, Номер 9(5), С. 524 - 524

Опубликована: Май 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Язык: Английский

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The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis

Acta Neuropathologica, Год журнала: 2019, Номер 137(5), С. 757 - 783

Опубликована: Март 7, 2019

Язык: Английский

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Glial cells in schizophrenia: a unified hypothesis

The Lancet Psychiatry, Год журнала: 2019, Номер 7(3), С. 272 - 281

Опубликована: Ноя. 6, 2019

Язык: Английский

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Copper signalling: causes and consequences

Cell Communication and Signaling, Год журнала: 2018, Номер 16(1)

Опубликована: Окт. 22, 2018

Copper-containing enzymes perform fundamental functions by activating dioxygen (O

Язык: Английский

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Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS

Cells, Год журнала: 2020, Номер 9(5), С. 1108 - 1108

Опубликована: Апрель 29, 2020

Microglial cells, the resident macrophages of central nervous system (CNS), exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell-damaging factors, they get transformed into an amoeboid releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species, and excytotoxic ATP glutamate. In addition, engulf pathogenic bacteria or debris phagocytose them. However, already resting/surveying microglia have number important physiological functions CNS; for example, shield small disruptions blood-brain barrier their processes, dynamically interact with synaptic structures, clear surplus synapses during development. neurodegenerative illnesses, aggravate original disease microglia-based compulsory neuroinflammatory reaction. Therefore, blockade this reaction improves outcome Alzheimer's Disease, Parkinson's multiple sclerosis, amyotrophic lateral etc. The function is regulated whole array purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, A2A, A3, targets endogenous ATP, ADP, adenosine. sequentially degraded ecto-nucleotidases 5'-nucleotidase enzymes to almost inactive inosine end product. appropriate selective agonists/antagonists well respective enzyme inhibitors may profoundly interfere microglial reconstitute homeostasis CNS disturbed neuroinflammation.

Язык: Английский

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Sepsis-Associated Encephalopathy: From Delirium to Dementia?

Journal of Clinical Medicine, Год журнала: 2020, Номер 9(3), С. 703 - 703

Опубликована: Март 5, 2020

Sepsis is a major cause of death in intensive care units worldwide. The acute phase sepsis often accompanied by sepsis-associated encephalopathy, which highly associated with increased mortality. Moreover, the chronic phase, more than 50% surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality life placing an immense burden on primary caregivers. Due to growing number survivors, these long-lasting are increasingly relevant. Despite high incidence clinical relevance, pathomechanisms stages encephalopathy only incompletely understood, no specific therapeutic options yet available. Here, we review emergence initial presentation impairment survivors summarize potentially contributing development encephalopathy.

Язык: Английский

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Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Июль 6, 2020

Abstract Astrocytic Ca 2+ signaling has been intensively studied in health and disease but not quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic signals the neocortex of awake naturally sleeping mice while monitoring neuronal activity, brain rhythms behavior. We show that exhibit distinct features across sleep-wake cycle are reduced sleep compared wakefulness. Moreover, increase precedes transitions from slow wave wakefulness, with a peak upon awakening exceeding levels whisking locomotion. Finally, genetic ablation important pathway impairs results increased number microarousals, abnormal rhythms, frequency state spindles. Our findings demonstrate essential role for regulating

Язык: Английский

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Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Язык: Английский

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Neuropathobiology of COVID-19: The Role for Glia

Frontiers in Cellular Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Ноя. 11, 2020

SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has a strong brain neurotropism via binding to receptor angiotensin-converting enzyme 2 expressed by neurones and glial cells, including astrocytes microglia. Systemic infection accompanies severe cases of COVID-19 also triggers substantial increase in circulating levels chemokines interleukins that compromise blood-brain barrier, enter parenchyma affect its defensive systems, Brain areas devoid barrier such as circumventricular organs are particularly vulnerable inflammatory mediators. The performance microglia, well immune cells required for health, is considered critical defining neurological damage outcome COVID-19. In this review, we discuss implication neuroinflammation, adaptive innate immunity, autoimmunity, astrocytic microglial homeostatic functions psychiatric aspects consequences SARS-CoV-2 during ageing, presence systemic comorbidities, exposed pregnant mother foetus will be specifically covered.

Язык: Английский

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Glial and myeloid heterogeneity in the brain tumour microenvironment

Nature reviews. Cancer, Год журнала: 2021, Номер 21(12), С. 786 - 802

Опубликована: Сен. 28, 2021

Язык: Английский

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