SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aβ phagocytosis DOI Creative Commons

Pei Ouyang,

Zhiyu Cai,

Jiaying Peng

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103064 - 103064

Published: Feb. 2, 2024

Amyloid-beta (Aβ) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise AD treatment. Here, we revealed that selenoprotein K (SELENOK), involved immune regulation potentially related to pathology, plays critical role microglial response, migration, phagocytosis. In vivo vitro studies corroborated SELENOK deficiency inhibits Aβ phagocytosis, exacerbating cognitive deficits 5xFAD mice, which are reversed by overexpression. Mechanistically, CD36 palmitoylation through DHHC6, regulating localization plasma membranes thus impacting was reduced brains patients mice with AD. Se supplementation promoted expression palmitoylation, enhancing phagocytosis mitigating progression. We have identified regulatory mechanisms from Se-dependent selenoproteins providing novel insights into potential therapeutic strategies involving selenoproteins.

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

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

Citations

237
The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets DOI Creative Commons

Alhamdu Adamu,

Shuo Li,

Fankai Gao

et al.

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

Citations

95
Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression DOI Creative Commons
Lucas Fornari Laurindo, Jefferson Aparecido Dias, Adriano Cressoni Araújo

et al.

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

Citations

47
Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First? DOI Creative Commons
Caterina Peggion, Tito Calì, Marisa Brini

et al.

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

Citations

26
Autophagy, aging, and age-related neurodegeneration DOI Creative Commons
Jennifer E. Palmer,

Niall Wilson,

Sung Min Son

et al.

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

Citations

21
JAK2/STAT3 as a new potential target to manage neurodegenerative diseases: An interactive review DOI
Siva Prasad Panda, Adarsh Kesharwani, Samaresh Datta

et al.

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

Published: March 15, 2024

Language: Английский

Citations

20
Roles of Cytokines in Alzheimer’s Disease DOI Open Access
Zilin Chen, Yekkuni L. Balachandran, Wai Po Chong

et al.

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

Citations

17
Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites DOI Creative Commons
Sen Li, Yuwei Cai, Tong Guan

et al.

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

Citations

17
Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases DOI Creative Commons
Leilei Chen, Qingqing Shen, Yingjuan Liu

et al.

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

Published: Feb. 2, 2025

Language: Английский

Citations

8
Targeting uric acid: a promising intervention against oxidative stress and neuroinflammation in neurodegenerative diseases DOI Creative Commons
Xu Lin, Chengwei Li,

Tiantian Wan

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 3, 2025

Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions biomarkers to address oxidative these conditions limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence a potential target diseases. Soluble UA stands out one most vital antioxidant compounds produced by human body, accounting for up 55% extracellular capacity neutralize free radicals. While there increasing evidence supporting neuroprotective properties Parkinson's disease Alzheimer's disease, gaps knowledge still exist regarding underlying mechanisms how effectively translate benefits into clinical practice. Moreover, current elevation therapy exhibits unstable properties, individual variability, even adverse effects, limiting its applications. This review consolidates recent advancements understanding exerts effects on diseases emphasizes dual roles managing neuroinflammation. Additionally, elucidates through which confers neuroprotection. Based this, underscores significance biomarker aims provide comprehensive therapeutic target, while also addressing possible challenges implementation.

Language: Английский

Citations

5