Advances in the Understanding of the Correlation Between Neuroinflammation and Microglia in Alzheimer’s Disease

ImmunoTargets and Therapy, Journal Year: 2024, Volume and Issue: Volume 13, P. 287 - 304

Published: June 1, 2024

Alzheimer's disease (AD) is a fatal neurodegenerative with subtle and progressive onset the most common type of dementia. However, its etiology pathogenesis have not yet been fully elucidated. The pathological manifestations AD include extraneuronal β-amyloid deposition (Aβ), intraneuronal tau protein phosphorylation leading to formation 'neurofibrillary tangles' (NFTs), neuroinflammation, loss brain neurons/synapses, glucose metabolism disorders. Current treatment approaches for primarily focus on 'Aβ cascade hypothesis abnormal aggregation hyperphosphorylation proteins', but shown limited efficacy. Therefore, there an ongoing need identify more effective targets AD. central nervous system (CNS) inflammatory response plays key role in occurrence development Neuroinflammation immune activated by glial cells CNS that usually occurs stimuli such as nerve injury, infection toxins or autoimmunity. ranks third prominent feature AD, following Aβ NFTs. In recent years, neuroinflammation microglia has increased due advancements genome-wide association studies (GWAS) sequencing technology. Furthermore, research validated pivotal microglia-mediated progression this article reviews latest progress triggered aiming provide new theoretical basis further exploring process development.

Language: Английский

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Microfluidics-enabled mesenchymal stem cell derived Neuron like cell membrane coated nanoparticles inhibit inflammation and apoptosis for Parkinson’s Disease

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 25, 2024

Abstract Parkinson’s disease (PD) is the second largest group of neurodegenerative diseases, and its existing drug treatments are not satisfactory. Natural cell membrane drugs used for homologous targeting to enhance efficacy. In this study, microfluidic electroporation chip prepared mesenchymal stem cell-derived neuron-like membrane-coated curcumin PLGA nanoparticles (MM-Cur-NPs) was synthesized explored therapeutic effect mechanism in PD. MM-Cur-NPs can protect neuron from damage, restore mitochondrial potential reduce oxidative stress vitro. PD mice, it also improve movement disorders damaged TH neurons. found be distributed brain metabolized with a delay within 24 h. After 1 h administration, were variety neurotransmitters significantly upregulated, such as dopamine. Differentially expressed genes RNA-seq enriched inflammation regulation, up-expression anti-inflammatory factors inhibited pro-inflammatory Mechanically, only neuronal apoptosis, inhibit microglial marker IBA-1 inflammation, but upregulate expression protein VDAC1 potential. This study proposes strategy provide neuroprotective effects through therapy

Language: Английский

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Increased expression of ER stress, inflammasome activation, and mitochondrial biogenesis-related genes in peripheral blood mononuclear cells in major depressive disorder

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Language: Английский

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Is Drp1 a link between mitochondrial dysfunction and inflammation in Alzheimer’s disease?

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: May 12, 2023

Recent advances highlight that inflammation is critical to Alzheimer Disease (AD) pathogenesis. Indeed, several diseases characterized by are considered risk factors for AD, such as type 2 diabetes, obesity, hypertension, and traumatic brain injury. Moreover, allelic variations in genes involved the inflammatory cascade AD. AD also mitochondrial dysfunction, which affects energy homeostasis of brain. The role dysfunction has been mostly neuronal cells. However, recent data demonstrating occurs cells, promoting secretion pro-inflammatory cytokines, turn induce neurodegeneration. In this review, we summarize finding supporting hypothesis inflammatory-amyloid describe demonstrate link between altered cascade. We focus summarizing Drp1, fission, showing Drp1 activation leads NLRP3 inflammasome, cascade, aggravates Amyloid beta (Ab) deposition tau-induced neurodegeneration, relevance pathway an early event

Language: Английский

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Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Dec. 19, 2023

Inflammasomes in astrocytes have been shown to play a crucial role the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's (AD). Cannabinoid Receptor 2(CB2R), G protein-coupled receptor (GPCR), is considered promising therapeutic target inflammation-related disorders. This study aims explore CB2R regulating NOD-like family pyrin domain containing 3 (NLRP3)-mediated neuroinflammation astrocytes.In an vivo animal model, specific targeting astrocytic was achieved by injecting CB2R-specific adenovirus (or fork head box g1(foxg1) adenovirus) knock down or administering agonists, inhibitors, etc., substantia nigra pars compacta (SNc) mice. A PD mouse model established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induction. Animal behavioral tests, western blot, immunofluorescence, other experiments were performed assess loss midbrain tyrosine hydroxylase (TH) neurons, activation astrocytes, NLRP3 pathway. Primary cultured vitro, inflammasomes activated 1-methyl-4-phenylpyridinium (MPP+) lipopolysaccharide (LPS) adenosine triphosphate (ATP). Western blot ELISA conducted release inflammatory factors. Transcriptomic sequencing CUT&RUN techniques employed regulation foxg1 binding site on autophagy molecule microtubule-associated protein 1 light chain beta (MAP1LC3B).Astrocytic knockdown impaired motor abilities MPTP-induced mice, exacerbated TH induced NLRP3/Caspase-1/interleukin (IL-1β) Activation significantly alleviated impairments mice while reducing deposition astrocytes. In vitro cell showed that attenuated NLRP3/Caspase-1/IL-1β pathway LPS + ATP MPP+. Additionally, it inhibited MAP1LC3B, increased levels, facilitated degradation through autophagy-lysosome pathway.Activation effectively mitigates NLRP3-mediated ameliorates characteristics represents potential for treating PD.

Language: Английский

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Cell-Type-Specific Mitochondrial Quality Control in the Brain: A Plausible Mechanism of Neurodegeneration

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14421 - 14421

Published: Sept. 22, 2023

Neurodegeneration is an age-dependent progressive phenomenon with no defined cause. Aging the main risk factor for neurodegenerative diseases. During aging, activated microglia undergo phenotypic alterations that can lead to neuroinflammation, which a well-accepted event in pathogenesis of Several common mechanisms are shared by genetically or pathologically distinct diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding translational dysfunction, autophagy activation. Progressive loss neuronal population due increased stress leads mostly accumulation dysfunctional mitochondria. Mitochondrial dysfunction excessive neuroinflammatory responses both sufficient induce pathology neurodegeneration. Therefore, quality control key determinant health survival cells brain. Research has been primarily focused demonstrate significance health, despite important contributions non-neuronal constitute significant portion brain volume. Moreover, morphology function distinctly diverse different tissues; however, little known about their molecular diversity among cell types. dynamics types markedly decide fate overall health; therefore, it not justifiable overlook active contribution facilitating health. In this review article, we aim discuss how remarkable highly synchronized connecting property keeping neurons healthy

Language: Английский

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Hyperglycemia‐induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(8)

Published: Aug. 1, 2024

Hyperglycemia-induced neuroinflammation significantly contributes to diabetic neuropathic pain (DNP), but the underlying mechanisms remain unclear.

Language: Английский

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Yin-Yang: two sides of extracellular vesicles in inflammatory diseases

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 27, 2024

The concept of Yin-Yang, originating in ancient Chinese philosophy, symbolizes two opposing but complementary forces or principles found all aspects life. This can be quite fitting the context extracellular vehicles (EVs) and inflammatory diseases. Over past decades, numerous studies have revealed that EVs exhibit dual sides, acting as both pro- anti-inflammatory agents, akin to Yin-Yang theory (i.e., sides a coin). has enabled serve potential indicators pathogenesis manipulated for therapeutic purposes by influencing immune pathways. review delves into recent advances understanding their regulation specific We shed light on current prospects engineering treating conditions. principle bestows upon them great as, therapeutic, preventive agents

Language: Английский

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From mitochondrial dysfunction to neuroinflammation in Parkinson’s disease: Pathogenesis and mitochondrial therapeutic approaches

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113015 - 113015

Published: Sept. 1, 2024

Language: Английский

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Protective role of mitophagy on microglia-mediated neuroinflammatory injury through mtDNA-STING signaling in manganese-induced parkinsonism

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 28, 2025

Manganese (Mn), the third most abundant transition metal in earth's crust, has widespread applications emerging field of organometallic catalysis and traditional industries. Excessive Mn exposure causes neurological syndrome resembling Parkinson's disease (PD). The pathogenesis PD is thought to involve microglia-mediated neuroinflammatory injury, with mitochondrial dysfunction playing a role aberrant microglial activation. In early stages PD, PINK1/Parkin-mediated mitophagy contributes inflammatory response via cGAS/STING signaling pathway. Suppression due excessive exacerbates neuronal injury. Moreover, leads damage cGAS-STING However, precise modulating neuroinflammation Mn-induced parkinsonism its underlying molecular mechanism remains unclear. Here, we observed that Mn-exposed mice exhibited neurobehavioral abnormalities detrimental activation, along increased apoptosis nerve cells, proinflammatory cytokines, intracellular ROS. Furthermore, vivo vitro experiments showed resulted dysfunction, manifested by ROS, decreased mass, membrane potential. Additionally, escalating dose, changed from activation suppression. This was evidenced levels LC3-II, PINK1, p-Parkin/Parkin, p62 protein expression level, as well colocalization between ATPB LC3B exposure. Upregulation urolithin A could mitigate indicated potential, improvements deficits attenuated Using single-nucleus RNA-sequencing (snRNA-seq) analysis mouse model, identified pathway potential neuroinflammation. associated an increase cytosolic mtDNA levels, which activate STING signaling. These findings point induction viable strategy alleviate through mtDNA-STING

Language: Английский

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