Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

Antioxidants, Journal Year: 2021, Volume and Issue: 10(9), P. 1479 - 1479

Published: Sept. 16, 2021

The pathogenesis of Alzheimer's disease involves β amyloid (Aβ) accumulation known to induce synaptic dysfunction and neurodegeneration. brain's vulnerability oxidative stress (OS) is considered a crucial detrimental factor in disease. OS Aβ are linked each other because induces OS, increases the deposition. Thus, answer question "which comes first: chicken or egg?" remains extremely difficult. In any case, evidence for primary occurrence AD attractive. indicates that long period gradual damage precedes results appearance clinical pathological symptoms, including deposition, neurofibrillary tangle formation, metabolic dysfunction, cognitive decline. Moreover, plays role many risk factors AD. begins years before its antioxidant treatment can be an important therapeutic target attacking

Language: Английский

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Activation and Role of Astrocytes in Ischemic Stroke

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Nov. 17, 2021

Ischemic stroke refers to the disorder of blood supply local brain tissue caused by various reasons. It has high morbidity and mortality worldwide. Astrocytes are most abundant glial cells in central nervous system (CNS). They responsible for homeostasis, nutrition, protection CNS play an essential role many diseases’ physiological pathological processes. After injury, astrocytes activated a protective through heterogeneous gradual changes their gene expression, morphology, proliferation, function, that is, reactive astrocytes. However, position always been controversial topic. Many studies have shown double-edged sword with both beneficial harmful effects. is worth noting different spatial temporal expression determines astrocytes’ functions. Here, we comprehensively review roles mechanisms after ischemic stroke. In addition, intracellular mechanism astrocyte activation also involved. More importantly, due complex cascade reaction action stroke, still difficult define. Still, there no doubt one critical factors mediating deterioration or improvement

Language: Английский

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Mitochondria: It is all about energy

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

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Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10572 - 10572

Published: Sept. 12, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it the most common cause of dementia and has no treatment. It characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal Neurofibrillary tangles (NFTs). Yet, those hallmarks do not explain full pathology seen with AD, suggesting involvement other mechanisms. Neuroinflammation could offer another explanation for progression disease. This review provides an overview recent advances on role immune cells' microglia astrocytes in neuroinflammation. In become reactive several mechanisms leading to release proinflammatory cytokines that further neuronal damage. We then provide updates neuroinflammation diagnostic markers investigational therapeutics currently clinical trials target

Language: Английский

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Astrocyte metabolism and signaling pathways in the CNS

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

Published: Sept. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Language: Английский

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Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 20, 2024

Abstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD loss dopaminergic neurons and presence aggregated α-synuclein, primarily in substantia nigra pars compacta (SNpc) midbrain. However, molecular mechanisms that underlie pathology different cell types not currently understood. Here, we present a single nucleus transcriptome analysis human post-mortem SNpc obtained from 15 sporadic cases 14 Controls. Our dataset comprises ∼84K nuclei, representing all major brain, allowing us to obtain transcriptome-level characterization these types. Importantly, identify multiple subpopulations for each type describe specific gene sets provide insights into differing roles subpopulations. findings reveal significant decrease neuronal cells samples, accompanied by an increase glial T cells. Subpopulation analyses demonstrate depletion tyrosine hydroxylase ( TH ) enriched astrocyte, microglia oligodendrocyte populations as well neurons, which are also depleted. Moreover, marker depleted identified 28 overlapping genes, including those associated with dopamine metabolism (e.g., ALDH1A1, SLC6A3 & SLC18A2 ). Overall, our study provides valuable resource understanding involved neuron degeneration responses PD, highlighting existence novel type-specific sets.

Language: Английский

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Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 504 - 504

Published: Jan. 24, 2024

Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves the production of lactate as end product glucose breakdown even presence adequate oxygen, is foundation for current interest cancer-cell-specific reprograming metabolic pathways. The renewed cell metabolism has now gone well beyond original effect related to other pathways that include amino acid metabolism, one-carbon pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since and acids constitute primary nutrients fuel altered transporters mediate transfer these their metabolites not only across plasma membrane but also mitochondrial lysosomal membranes have become an integral component expansion effect. In this review, we focus on interplay between facilitates reprogramming, a hallmark cells. beneficial outcome recent understanding unique signature surrounding identification novel drug targets development new generation therapeutics treat cancer.

Language: Английский

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Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit

Cells, Journal Year: 2022, Volume and Issue: 11(5), P. 813 - 813

Published: Feb. 25, 2022

The neurovascular unit (NVU) is a conceptual framework that has been proposed to better explain the relationships between neural cells and blood vessels in human brain, focused mainly on brain gray matter. major components of NVU are neurons, astrocytes (astroglia), microvessels, pericytes, microglia. In addition, we believe oligodendrocytes should also be included as an indispensable component white Of all these components, particular have attracted interest researchers because their unique anatomical location; interposed neurons microvessels brain. Their location suggests might regulate cerebral flow (CBF) response neuronal activity, so ensure adequate supply glucose oxygen meet metabolic demands neurons. fact, adult which accounts for only 2% entire body weight, consumes approximately 20–25% total amount consumed by whole body. needs continuous essential energy sources through CBF, there practically no stores or brain; both acute chronic cessation CBF can adversely affect functions. another important putative function elimination heat waste materials produced activity. Recent evidence play pivotal roles not supplying glucose, but fatty acids amino Loss astrocytic support expected lead malfunction whole, underlies numerous neurological disorders. this review, shall focus historical recent findings with regard contributions NVU.

Language: Английский

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Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(1), P. 170 - 170

Published: Jan. 17, 2022

Oxidative stress and neuroinflammation are common bases for disease onset progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting dopamine depletion, pathogenesis differs between hereditary solitary forms often unclear. addition to pathogenicity alpha-synuclein as a pathological marker, involvement itself its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, hallmark neurons, essential homeostatic maintenance adequate concentrations synaptic cleft, but it imposes burden on mitochondrial oxidative glucose metabolism, leading reactive oxygen species production. Astrocytes provide endogenous neuroprotection brain producing releasing antioxidants response stress. Additionally, protective function astrocytes can be modified microglia. Some types microglia themselves thought exacerbate pro-inflammatory factors (M1 microglia). Although these inflammatory may further trigger conversion astrocytes, induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both express receptors, upregulated presence neuroinflammation. The anti-inflammatory receptor stimulation also attracting attention because functions greatly affected depletion therapeutic replacement disease. this review article, we will focus antioxidative their synergism dopamine.

Language: Английский

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The gut microbiota‐astrocyte axis: Implications for type 2 diabetic cognitive dysfunction

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(S1), P. 59 - 73

Published: Jan. 4, 2023

Abstract Background Diabetic cognitive dysfunction (DCD) is one of the most insidious complications type 2 diabetes mellitus, which can seriously affect ability to self‐monitoring blood glucose and quality life in elderly. Previous pathological studies have focused on neuronal dysfunction, characterized by extracellular beta‐amyloid deposition intracellular tau hyperphosphorylation. In recent years, astrocytes been recognized as a potential therapeutic target for important participants central control metabolism. The disorder gut microbiota their metabolites linked series metabolic diseases such mellitus. imbalance intestinal flora has effect promoting occurrence deterioration several diabetes‐related complications. Gut microbes drive astrocyte activation. Aims We reviewed progress DCD related “gut microbiota‐astrocyte” axis terms peripheral inflammation, blood–brain barrier (BBB) systemic brain energy metabolism disorders deepen research explore targets. Conclusion “Gut axis, unique bidirectional crosstalk brain‐gut mediates intermediate process neurocognitive secondary

Language: Английский

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