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

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 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.

Language: Английский

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From Synapses to Circuits, Astrocytes Regulate Behavior

Frontiers in Neural Circuits, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 4, 2022

Astrocytes are non-neuronal cells that regulate synapses, neuronal circuits, and behavior. ensheath synapses to form the tripartite synapse where astrocytes influence formation, function, plasticity. Beyond synapse, recent research has revealed astrocyte influences on nervous system extend modulation of circuitry Here we review findings active role in behavioral with a focus vivo studies, primarily mice. Using tools acutely manipulate astrocytes, such as optogenetics or chemogenetics, studies reviewed here have demonstrated causal for sleep, memory, sensorimotor behaviors, feeding, fear, anxiety, cognitive processes like attention flexibility. Current future directions astrocyte-specific manipulation, including methods probing heterogeneity, discussed. Understanding contribution circuit activity organismal behavior will be critical toward understanding how function gives rise

Language: Английский

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Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 20, 2023

Autism spectrum disorder (ASD) is a common neurodevelopmental with onset in childhood. The mechanisms underlying ASD are unclear. In recent years, the role of microglia and astrocytes has received increasing attention. Microglia prune synapses or respond to injury by sequestrating site expressing inflammatory cytokines. Astrocytes maintain homeostasis brain microenvironment through uptake ions neurotransmitters. However, molecular link between and, remains unknown. Previous research shown significant ASD, reports increased numbers reactive postmortem tissues animal models ASD. Therefore, an enhanced understanding roles essential for developing effective therapies. This review aimed summarize functions their contributions

Language: Английский

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Astrocyte-secreted neurocan controls inhibitory synapse formation and function

Neuron, Journal Year: 2024, Volume and Issue: 112(10), P. 1657 - 1675.e10

Published: April 3, 2024

Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an protein. After secretion from astrocytes, is cleaved into N- C-terminal fragments. We found these fragments have distinct localizations in extracellular matrix. The fragment localizes to controls cortical function. Neurocan knockout mice lacking whole protein or only its domain reduced numbers Through super-resolution microscopy, vivo proximity labeling TurboID, astrocyte-specific rescue approaches, discovered somatostatin-positive regulates their formation. Together, our results unveil a mechanism through which astrocytes control circuit-specific mammalian brain.

Language: Английский

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Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(5), P. 607 - 616

Published: April 28, 2022

Language: Английский

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Microglia-mediated synaptic pruning as a key deficit in neurodevelopmental disorders: Hype or hope?

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 79, P. 102674 - 102674

Published: Jan. 17, 2023

There is a consensus in the field that microglia play prominent role neurodevelopmental processes like synaptic pruning and neuronal network maturation. Thus, current momentum of associating deficits with disorders (NDDs) emerged. This concept challenged by rodent studies clinical data. Intriguingly, reduced numbers or altered microglial functions do not necessarily lead to overt NDD phenotypes, neuropsychiatric symptoms seem develop primarily adulthood. Hence, it remains open for discussion whether are truly indispensable healthy neurodevelopment. Here, we critically discuss highlight area- age dependency. We propose an updated model microglia-mediated context NDDs potential targeting treatment these disorders.

Language: Английский

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Myelin in Alzheimer’s disease: culprit or bystander?

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: March 31, 2023

Alzheimer's disease (AD) is a neurodegenerative disorder with neuronal and synaptic losses due to the accumulation of toxic amyloid β (Αβ) peptide oligomers, plaques, tangles containing tau (tubulin-associated unit) protein. While familial AD caused by specific mutations, sporadic more common appears result from complex chronic brain neuroinflammation mitochondriopathies, inducing free radicals' accumulation. In aged brain, mutations in DNA several unfolded proteins participate amyloidosis response effect on myelin sheath axons, leading cognitive deficits dementia. Αβ peptides are most frequent form oligomers. Accumulations misfolded during years alters different metabolic mechanisms, induce inflammatory immune responses consequences cells. Myelin composition architecture may appear be an early target for activity Aβ others hydrophobic proteins. this work, we describe possible role alterations genesis onset symptomatology. We propose that some pathophysiological clinical forms arise structural disorders processes myelination/demyelination regions where non-functional important. these forms, primacy deleterious would matter questioning initiating neuropathology primarily fact dysmyelination.

Language: Английский

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Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation

Molecules, Journal Year: 2022, Volume and Issue: 27(2), P. 341 - 341

Published: Jan. 6, 2022

Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological in absence of evident infection. This condition has been linked broad spectrum age-related disorders various organs including brain. represents highly significant risk factor for development progression conditions, neurodegenerative diseases which are characterized by progressive dysfunction degeneration neurons brain peripheral nervous system. Curcumin widely studied polyphenol isolated from Curcuma longa with variety pharmacologic properties. It well-known its healing properties extensively Asian medicine treat illness conditions. The number studies suggest beneficial effects curcumin on pathologies increasing. able inhibit formation reactive-oxygen species other pro-inflammatory mediators believed play pivotal role many diseases. recently proposed as potential useful remedy against ageing. In light this, our current review aims discuss positive possibility control inflammaging emphasizing possible modulation processes

Language: Английский

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Double stochastic resonance in neuronal dynamics due to astrocytes

Chaos Solitons & Fractals, Journal Year: 2023, Volume and Issue: 168, P. 113140 - 113140

Published: Jan. 22, 2023

Language: Английский

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Identification of ligand–receptor pairs that drive human astrocyte development

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(8), P. 1339 - 1351

Published: July 17, 2023

Language: Английский

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