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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Tissue-specific macrophages: how they develop and choreograph tissue biology

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Genetics and Pathogenesis of Parkinson's Syndrome

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 95 - 121

Published: Sept. 13, 2022

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops virtually unique form of syndrome. Clinical manifestations consist variable motor nonmotor features, myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central peripheral nervous systems, distribution varies pathologies modify PD or trigger similar manifestations. Nearly all influenced. More than 100 genes genetic loci have been identified, cases likely arise from interactions among many common rare variants. Despite its complex architecture, insights experimental dissection coalesce reveal unifying biological themes, including synaptic, lysosomal, mitochondrial, andimmune-mediated mechanisms pathogenesis. This emerging understanding syndrome, coupled advances in biomarkers targeted therapies, presages successful precision medicine strategies.

Language: Английский

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Transforming the understanding of brain immunity

Science, Journal Year: 2023, Volume and Issue: 380(6640)

Published: April 6, 2023

Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.

Language: Английский

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Programming axonal mitochondrial maintenance and bioenergetics in neurodegeneration and regeneration

Neuron, Journal Year: 2022, Volume and Issue: 110(12), P. 1899 - 1923

Published: April 16, 2022

Language: Английский

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The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability

Cell, Journal Year: 2022, Volume and Issue: 185(12), P. 2035 - 2056.e33

Published: June 1, 2022

Alpha-synuclein (αS) is a conformationally plastic protein that reversibly binds to cellular membranes. It aggregates and genetically linked Parkinson's disease (PD). Here, we show αS directly modulates processing bodies (P-bodies), membraneless organelles function in mRNA turnover storage. The N terminus of αS, but not other synucleins, dictates mutually exclusive binding either membranes or P-bodies the cytosol. associates with multiple decapping proteins close proximity on Edc4 scaffold. As pathologically accumulates, aberrant interaction occurs at expense physiologic decapping-module interactions. decay kinetics within PD-relevant pathways are correspondingly disrupted PD patient neurons brain. Genetic modulation P-body components alters toxicity, human genetic analysis lends support disease-relevance these Beyond revealing an unexpected aspect pathology, our data highlight versatility high intrinsic disorder.

Language: Английский

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Controlled Activation of TRPV1 Channels on Microglia to Boost Their Autophagy for Clearance of Alpha‐Synuclein and Enhance Therapy of Parkinson's Disease

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(11)

Published: Jan. 13, 2022

Parkinson's disease (PD) is characterized with accumulation of Lewy bodies a major component fibrillar alpha-synuclein (α-syn). Herein, boosting PD therapeutic efficacy by enhancing the autophagy microglia to phagocytose and degrade α-syn via controlled opening their surface TRPV1 channels rationally designed photothermal nanoagent reported. The Cu2-x Se-anti-TRPV1 nanoparticles (CS-AT NPs) are fabricated target open under second near infrared (NIR-II) laser irradiation cause influx Ca2+ activate ATG5 /CaMKK2/AMPK/mTOR signaling pathway, which promote phagocytosis degradation α-syn. CS-AT NPs efficiently delivered focused ultrasound into striatum mice high expression receptors. athletic ability treated NIR-II significantly improved due phagocytotic clearance enhanced autophagy. enzyme tyrosine hydroxylase, ionized calcium binding adapter protein 1, glial fibrillary acidic protein, pSer129-α-syn (p-α-syn) almost recovered normal levels healthy mice. This study provides insights activation microglial targeting ion improve treatment other neurodegenerative diseases.

Language: Английский

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Iron, Neuroinflammation and Neurodegeneration

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7267 - 7267

Published: June 30, 2022

Disturbance of the brain homeostasis, either directly via formation abnormal proteins or cerebral hypo-perfusion, indirectly peripheral inflammation, will activate microglia to synthesise a variety pro-inflammatory agents which may lead inflammation and cell death. The cytokines induce changes in iron responsible for maintaining such that increased amounts be deposited cells brain. generation reactive oxygen nitrogen species, is involved inflammatory process, can significantly affect metabolism their interaction with iron-regulatory (IRPs). This underlies importance ensuring maintained form kept under control; hence, elegant mechanisms have become increasingly well understood regulating homeostasis. Therapeutic approaches minimise toxicity include N-acetyl cysteine, non-steroidal anti-inflammatory compounds chelation.

Language: Английский

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Neuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities

Cells, Journal Year: 2022, Volume and Issue: 11(18), P. 2908 - 2908

Published: Sept. 17, 2022

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Clinically, it characterized by a progressive degeneration of dopaminergic neurons (DAn), resulting in severe motor complications. Preclinical and clinical studies have indicated that neuroinflammation can play role PD pathophysiology, being associated with its onset progression. Nevertheless, several key points concerning neuroinflammatory process remain to be answered. Bearing this mind, present review, we cover impact on exploring inflammatory cells (i.e., microglia astrocytes) interconnections between brain peripheral system. Furthermore, discuss both innate adaptive immune responses regarding pathology explore gut-brain axis communication influence progression disease.

Language: Английский

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