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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The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 12, 2024

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.

Language: Английский

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Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Language: Английский

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Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 240 - 240

Published: Feb. 16, 2024

Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these commonly feature chronic neuroinflammation hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction protein aggregation can mutually contribute to activation neuroinflammatory response thus onset progression disorders. In present review, we discuss contribution aetiology NDs, highlighting new potential therapeutic targets be identified tackle neurodegenerative processes alleviate pathologies.

Language: Английский

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Autophagy, aging, and age-related neurodegeneration

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance toxic proteins, proinflammatory molecules, dysfunctional organelles. inhibition also induces neuronal glial senescence, phenomenon occurs with increasing age non-diseased brains as well response to stresses. However, aging mutations impair autophagy. This creates potentially detrimental feedback loop whereby accumulation these disease-associated impairs their autophagic clearance, facilitating further aggregation. Thus, understanding how interacts aging, neurodegenerative diseases temporal, cellular, genetic context important for future clinical application autophagy-modulating therapies neurodegeneration.

Language: Английский

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Driving factors of neuronal ferroptosis

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(7), P. 535 - 546

Published: Feb. 23, 2024

Language: Английский

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JAK2/STAT3 as a new potential target to manage neurodegenerative diseases: An interactive review

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 970, P. 176490 - 176490

Published: March 15, 2024

Language: Английский

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Roles of Cytokines in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5803 - 5803

Published: May 26, 2024

The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic that plays pivotal role in pathogenesis progression Alzheimer’s disease (AD). Of particular focus are group signaling molecules facilitate communication among cells contribute to inflammation AD. Extensive research has shown dysregulated secretion certain cytokines (IL-1β, IL-17, IL-12, IL-23, IL-6, TNF-α) promotes neuroinflammation exacerbates neuronal damage However, anti-inflammatory (IL-2, IL-3, IL-33, IL-35) also secreted during AD onset progression, thereby preventing neuroinflammation. This review summarizes involvement pro- pathology discusses their therapeutic potential.

Language: Английский

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Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: July 7, 2024

With the increasing of aging population and consumption high-fat diets (HFD), incidence Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in prevention AD, as oxidative stress neuroinflammation are two hallmarks AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain levels Aβ p-Tau. Examination gut microbiota suggested improvement composition HFD mice after QA treatment. Metabolomic analysis significant increase microbial tryptophan metabolites indole-3-acetic (IAA) kynurenic (KYNA) by QA. In addition, IAA KYNA negative correlation with pro-inflammatory factors indicators. Further experiments on proved could reproduce effects suppress inflammation decrease Transcriptomics administration revealed inhibition DR3/IKK/NF-κB signaling pathway IAA. conclusion, this study demonstrated counteract regulating inflammatory via metabolites.

Language: Английский

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Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 2, 2025

Language: Английский

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