Microglial activation states and their implications for Alzheimer's Disease

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер 12(1), С. 100013 - 100013

Опубликована: Янв. 1, 2025

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) tau protein in brain. Microglia, key immune cells central nervous system, play an important role AD development progression, primarily through their responses to Aβ NFTs. Initially, microglia can clear Aβ, but AD, activation overwhelms protective mechanisms, leading sustained neuroinflammation that enhances plaque toxicity, setting off damaging cycle affects neurons, astrocytes, cerebral vasculature, other microglia. Current treatments have been largely ineffective, though emerging immunotherapies focusing on removal show promise, often overlook neuroinflammation. Activated display complex range phenotypes be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe significant overlap between states. strongly induce inflammatory activity, triggering production reactive oxygen species, cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, impaired clearance. These processes contribute neural tissue loss, manifesting as cognitive decline such executive function memory. Conversely, exerts neuroprotective effects suppressing pathways releasing neurotrophic factors aid neuron repair protection. Induction states may offer dual therapeutic approach address both AD. This suggests potential strategies modulate microglial phenotypes, aiming restore functions mitigate disease progression simultaneously targeting inflammation pathology.

Язык: Английский

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Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

Brain Sciences, Год журнала: 2024, Номер 14(6), С. 558 - 558

Опубликована: Май 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Язык: Английский

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Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Cells, Год журнала: 2024, Номер 13(6), С. 474 - 474

Опубликована: Март 7, 2024

Parkinson’s disease (PD) is a progressive neurodegenerative characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) the primary neurotransmitter involved in this disease, but cholinergic imbalance has been implicated. Current intervention PD focused on replenishing central DA, which provides remarkable temporary symptomatic relief does not address neuronal loss progression of disease. It well established nicotinic receptors (nAChRs) can regulate DA release nicotine itself may have neuroprotective effects. Recent studies identified nAChRs nonneuronal cell types, including glial cells, where they inflammatory responses. Given crucial role neuroinflammation dopaminergic degeneration involvement microglia astrocytes response, provide novel therapeutic target prevention and/or treatment PD. In review, following brief discussion PD, we focus cells and, specifically, their pathology treatment.

Язык: Английский

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Roles of Microglia in Neurodegenerative Diseases

Yonago acta medica, Год журнала: 2024, Номер 67(1), С. 1 - 8

Опубликована: Янв. 1, 2024

In recent years, microglia have attracted attention owing to their roles in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis. Microglia, which are brain-resident macrophages, not only act immune cells but also perform other functions the body. Interestingly, they exert contrasting effects on different diseases. addition previously reported M1 (toxic) M2 (protective) types, now include disease-associated a more elaborate classification. Understanding this detailed classification is necessary elucidate association between review, we discuss diverse of diseases highlight potential therapeutic targets.

Язык: Английский

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Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Опубликована: Янв. 31, 2024

Parkinson’s disease (PD) is a progressive neurodegenerative characterized by resting tremor, bradykinesia, rigidity, postural instability, that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) the primary neurotransmitter involved in this disease, but cholinergic imbalance has been implicated. Current intervention PD focused on replenishing central DA, which provides remarkable temporary symptomatic relief does not address neuronal losss and progression of disease. It well established nicotinic receptors (nAChRs) can regulate DA release nicotine itself may have neuroprotective effects. Recent studies identified nAChRs nonneuronal cell types including glial cells, where they inflammatory responses. Given crucial role neuroinflammation dopaminergic degeneration, involvement microglia astrocytes response, provide novel therapeutic target prevention and/or treatment PD. In review, following brief discussion PD, we focus cells specifically their pathology treatment.

Язык: Английский

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CCL17/CCR4 Axis Promotes Hematoma Clearance via ERK/AP1/SRA‐Mediated Microglial Polarization After Intracerebral Hemorrhage

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

Our previous studies demonstrated that CCL17 and its receptor CCR4 play crucial roles in neuroinflammation microglial activation following intracerebral hemorrhage (ICH). However, the specific mechanisms by which CCL17/CCR4 axis regulates polarization hematoma clearance remain unclear. This study investigates how signaling pathway modulates phenotype transition enhances resolution after ICH, building upon our earlier findings showing CCR4's involvement neuroinflammatory responses. Using CRISPR-mediated disruption overexpression approaches a mouse ICH model, we examined neurological outcomes, inflammatory responses, volumes. We further evaluated therapeutic potential of recombinant administration. The downstream ERK pathway's role CCL17/CCR4-mediated function was investigated through pharmacological inhibition. knockout exacerbated deficits, increased neuroinflammation, enlarged hematomas. In contrast, enhancing expression or administering improved functional recovery provided neuroprotection. Mechanistically, activated ERK/AP1/SRA pathway, promoting anti-inflammatory, phagocytic polarization, evidenced CD206 SRA expression. inhibition reversed these protective effects. extend work revealing pathway-mediated polarization. mechanism represents promising target for treatment.

Язык: Английский

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Targeting Neuroinflammation in Preterm White Matter Injury: Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes

Cellular and Molecular Neurobiology, Год журнала: 2025, Номер 45(1)

Опубликована: Март 12, 2025

Neuroinflammation is a key factor in the development of preterm white matter injury (PWMI), leading to glial cell dysfunction, arrest oligodendrocyte maturation, and long-term neurological damage. As potential therapeutic strategy, mesenchymal stem cells (MSCs) exhibit significant immunomodulatory regenerative potential. Recent studies suggest that primary mechanism MSC action their paracrine effects, particularly mediated by extracellular vesicles, with MSC-derived exosomes (MSC-Exos) being mediators. MSC-Exos, enriched lipids, proteins, nucleic acids, regulate neuroinflammation modulating activity influencing signaling pathways associated inflammation repair. Preclinical evidence has indicated MSC-Exos can suppress activation microglia astrocytes, promote enhance myelination, highlighting as cell-free treatment for PWMI. However, there are paucity comprehensive reviews on how PWMI through specific pathways. This review aims summarize which modulate discuss challenges clinical application MSC-Exos-based therapies.

Язык: Английский

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The dual role of microglia in Alzheimer’s disease: from immune regulation to pathological progression

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Март 27, 2025

Alzheimer’s disease (AD) is a widespread neurodegenerative disorder and one of the major challenges for public health. Despite extensive research, role microglia in AD remains complex dual. The aim this review to summarize most recent advances research regarding dual concerning both immunomodulation pathological progression by considering mechanisms activation microglia, effects on Aβ clearance, tau pathology, impacts due genetic variations microglial functions. Among these findings are status M1 M2 phenotypes, crucial that variants like TREM2 have modulating response microglia. This describes how modulation signaling pathway might be exploited therapeutically treatment underlines relevance personalized medicine approach.

Язык: Английский

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Microglia efferocytosis: an emerging mechanism for the resolution of neuroinflammation in Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Март 30, 2025

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by significant neuroinflammatory responses. Microglia, the immune cells of central nervous system, play crucial role in pathophysiology AD. Recent studies have indicated that microglial efferocytosis an important mechanism for clearing apoptotic and cellular debris, facilitating resolution neuroinflammation. This review summarizes biological characteristics microglia mechanisms underlying efferocytosis, including factors signaling pathways regulate interactions between other influence this process, neuroinflammation Furthermore, we explore AD from three perspectives: its impact on clearance amyloid plaques, regulation neuroinflammation, effects neuroprotection. Finally, summarize current research status enhancing to alleviate improve AD, as well future challenges approach therapeutic strategy

Язык: Английский

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Role of Achyranthes aspera in neurodegenerative diseases: current evidence and future directions

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 9, 2025

Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due complex pathogenesis limited efficacy therapeutic drugs, these have attracted significant attention. Achyranthes aspera , belongs family Amaranthaceae, has been extensively used in traditional folk medicines for treatment various ailments. Modern research revealed that possesses pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, anti-aging. Furthermore, neuroprotective effects confirmed numerous scientific studies. This review focuses on primary mechanisms prevention neurodegenerative diseases, as well potential application prospects. aims provide insights into clinical applications directions diseases.

Язык: Английский

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