Role of neuroinflammation in neurodegeneration development

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

Published: July 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Language: Английский

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Polystyrene nanoplastics penetrate across the blood-brain barrier and induce activation of microglia in the brain of mice

Chemosphere, Journal Year: 2022, Volume and Issue: 298, P. 134261 - 134261

Published: March 14, 2022

Language: Английский

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Biomarker of Neuroinflammation in Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4148 - 4148

Published: April 8, 2022

Parkinson’s disease (PD) is caused by abnormal accumulation of α-synuclein in dopaminergic neurons the substantia nigra, which subsequently causes motor symptoms. Neuroinflammation plays a vital role pathogenesis neurodegeneration PD. This neuroinflammatory involves activation microglia, upregulation proinflammatory factors, and gut microbiota. In this review, we summarized recent findings on detection PD using inflammatory biomarkers, such as interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor (TNF)-α; regulated upon activation, normal T cell expressed presumably secreted (RANTES) high-sensitivity c-reactive protein (hsCRP); radiotracers [11C]PK11195 [18F]-FEPPA, well monitoring progression treatment response. Many PD-causing mutations SNCA, LRRK2, PRKN, PINK1, DJ-1 are also associated with neuroinflammation. Several anti-inflammatory medications, including nonsteroidal drugs (NSAID), inhibitors TNF-α NLR family pyrin domain containing 3 (NLRP3), agonists nuclear erythroid 2-related 2 (NRF2), peroxisome proliferator-activated receptor gamma (PPAR-γ), steroids, have demonstrated neuroprotective effects vivo or vitro models. Clinical trials applying objective biomarkers required to investigate therapeutic potential medications for

Language: Английский

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The NLRP3 inflammasome: contributions to inflammation-related diseases

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: June 27, 2023

The NOD-like receptor protein 3 (NLRP3) inflammasome is a complex that regulates innate immune responses by activating caspase-1 and the inflammatory cytokines interleukin (IL)-1β IL-18. Multiple studies have demonstrated importance of NLRP3 in development inflammation-related diseases, including arthritis, Alzheimer's disease, bowel other autoimmune autoinflammatory diseases. This review first explains activation regulatory mechanism inflammasome. Secondly, we focus on role various Finally, look forward to new methods for targeting treat provide ideas clinical treatment.

Language: Английский

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Microglia Mediated Neuroinflammation in Parkinson’s Disease

Cells, Journal Year: 2023, Volume and Issue: 12(7), P. 1012 - 1012

Published: March 25, 2023

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in elderly. Tremor, shaking, movement problems, and difficulty with balance coordination are among hallmarks, dopaminergic neuronal loss substantia nigra pars compacta of brain aggregation intracellular protein α-synuclein pathological characterizations. Neuroinflammation has emerged as an involving mechanism at initiation development PD. It a complex network interactions comprising immune non-immune cells addition to mediators response. Microglia, resident macrophages CNS, take on leading role regulating neuroinflammation maintaining homeostasis. Under normal physiological conditions, they exist “homeostatic” but upon stimuli, switch “reactive state”. Pro-inflammatory (M1) anti-inflammatory (M2) phenotypes used classify microglial activity each phenotype having its own markers released mediators. When M1 microglia persistent, will contribute various inflammatory diseases, including such In this review, we focus mediated PD also signaling pathways, receptors, involved process, presenting studies that associate microglia-mediated inflammation A better understanding important seeking new therapies for possibly other diseases.

Language: Английский

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Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson’s disease

Inflammation Research, Journal Year: 2023, Volume and Issue: 72(3), P. 443 - 462

Published: Jan. 4, 2023

Language: Английский

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The link between neuroinflammation and the neurovascular unit in synucleinopathies

Science Advances, Journal Year: 2023, Volume and Issue: 9(7)

Published: Feb. 15, 2023

The neurovascular unit (NVU) is composed of vascular cells, glial and neurons. As a fundamental functional module in the central nervous system, NVU maintains homeostasis microenvironment integrity blood-brain barrier. Disruption interactions among its components are involved pathophysiology synucleinopathies, which characterized by pathological accumulation α-synuclein. Neuroinflammation contributes to including Parkinson's disease, multiple system atrophy, dementia with Lewy bodies. This review aims summarize neuroinflammatory response cells NVU. We also neuroinflammation context cross-talk between pericytes, microglia astroglia. Last, we discuss how α-synuclein affects influences aggregation spread analyze different properties synucleinopathies.

Language: Английский

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The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

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

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

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Signaling pathways in macrophages: molecular mechanisms and therapeutic targets

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Sept. 11, 2023

Abstract Macrophages play diverse roles in development, homeostasis, and immunity. Accordingly, the dysfunction of macrophages is involved occurrence progression various diseases, such as coronavirus disease 2019 atherosclerosis. The protective or pathogenic effect that exert different conditions largely depends on their functional plasticity, which regulated via signal transduction Janus kinase–signal transducer activator transcription, Wnt Notch pathways, stimulated by environmental cues. Over past few decades, molecular mechanisms signaling pathways have been gradually elucidated, providing more alternative therapeutic targets for diseases treatment. Here, we provide an overview basic physiology expound regulatory within them. We also address crucial role pathogenesis including autoimmune, neurodegenerative, metabolic, infectious cancer, with a focus advances macrophage‐targeted strategies exploring modulation components regulators pathways. Last, discuss challenges possible solutions therapy clinical applications. hope this comprehensive review will directions further research targeting macrophage are promising to improve efficacy

Language: Английский

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The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: April 25, 2022

For decades, it has been widely believed that the blood–brain barrier (BBB) provides an immune privileged environment in central nervous system (CNS) by blocking peripheral cells and humoral factors. This view revised recent years, with increasing evidence revealing plays a critical role regulating CNS homeostasis disease. Neurodegenerative diseases are characterized progressive dysfunction loss of neurons CNS. An number studies have focused on connection between neurodegenerative diseases. On one hand, peripherally released cytokines can cross BBB, cause direct neurotoxicity contribute to activation microglia astrocytes. other also infiltrate brain participate progression neuroinflammatory high morbidity disability rate, yet there no effective therapies stop or reverse their progression. In neuroinflammation received much attention as therapeutic target for many this review, we highlight emerging systems diseases, well interactions. A better understanding may improve strategies

Language: Английский

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