Interaction of Microglia and Astrocytes in the Neurovascular Unit

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Июль 8, 2020

The interaction between microglia and astrocytes significantly influences neuroinflammation. Microglia/astrocytes, part of the neurovascular unit (NVU), are activated by various brain insults. local extracellular intracellular signals determine their characteristics switch phenotypes. Microglia into two polarization states: pro-inflammatory phenotype (M1 A1) anti-inflammatory (M2 A2). During neuroinflammation, induced stroke or lipopolysaccharides, more sensitive to pathogens damage, thus initially M1 phenotype, produce common inflammatory such as IL- 1 TNF-α trigger reactive A1 phenotype. These can be amplified not only self-feedback loop microglial activation, but also unique anatomy structure astrocytes. As pathology further progresses, resulting in environmental changes, M1-like M2 crosstalk with A2. While communicate simultaneously neurons blood vessels maintain function blood-brain barrier (BBB), subtle changes may identified responded astrocytes, possibly transferred microglia. Although both have different functional characteristics, they achieve immune "optimization" through mutual communication cooperation NVU build a cascaded network amplification.

Язык: Английский

---

Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(14), С. 3380 - 3380

Опубликована: Июль 10, 2019

Alzheimer’s disease (AD), which is characterized by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles, accompanied neurodegeneration, most common form age-related neurodegenerative disease. Parkinson’s (PD) second after AD, early prominent loss dopaminergic neurons in substantia nigra pars compacta. As currently available treatments are not able to significantly alter progression these diseases, successful therapeutic preventive interventions strongly needed. In course our survey substances from natural resources having anti-dementia neuroprotective activity, we found nobiletin, a polymethoxylated flavone peel Citrus depressa. Nobiletin improved cognitive deficits pathological features such as Aβ pathology, hyperphosphorylation tau, oxidative stress, animal models AD. addition, nobiletin motor PD models. These observations suggest that has potential become novel drug for treatment prevention diseases AD PD.

Язык: Английский

---

Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Март 19, 2023

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disease, with the characteristics of neurofibrillary tangle (NFT) and senile plaque (SP) formation. Although great progresses have been made in clinical trials based on relevant hypotheses, these studies are also accompanied by emergence toxic side effects, it an urgent task to explore underlying mechanisms for benefits prevent treat AD. Herein, animal experiments few trials, neuroinflammation AD characterized long-term activation pro-inflammatory microglia NOD-, LRR- pyrin domain-containing protein 3 (NLRP3) inflammasomes. Damaged signals from periphery within brain continuously activate microglia, thus resulting constant source inflammatory responses. The response exacerbates endoplasmic reticulum oxidative stress which triggers microglia-dependent immune responses, ultimately leading occurrence deterioration In this review, we systematically summarized sorted out that exercise ameliorates directly indirectly regulating central nervous system promoting hippocampal neurogenesis provide new direction exploring activity

Язык: Английский

---

The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Март 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Язык: Английский

---

Exercise therapy to prevent and treat Alzheimer’s disease

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Авг. 4, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative in the elderly with dementia, memory loss, and severe cognitive impairment that imposes high medical costs on individuals. The causes of AD include increased deposition amyloid beta (Aβ) phosphorylated tau, age, mitochondrial defects, neuroinflammation, decreased synaptic connections, nerve growth factors (NGF). While animals moderate-intensity exercise restores hippocampal amygdala through levels p-AKT, p-TrkB, p-PKC Aβ, tau phosphorylation, precursor proteins (APP) AD. Aerobic (with an intensity 50–75% VO2 max) prevents volume reduction, spatial learning reduction increasing flexibility. Exercise training induces binding brain-derived neurotrophic factor (BDNF) to TrkB NGF TrkA induce cell survival neuronal plasticity. After aerobic high-intensity interval training, increase VEGF, angiopoietin 1 2, NO, tPA, HCAR1 cerebral vessels blood flow angiogenesis cerebellum, motor cortex, striatum, hippocampus. In hippocampus, decreases fragmentation, DRP1, FIS1, improving OPA1, MFN1, MFN2, morphology. humans, acute as anti-inflammatory condition IL-6 such IL-1RA IL-10. Moderate-intensity also inhibits inflammatory markers IFN-γ, IL-1β, IL-6, CRP, TNF-α, sTNFR1, COX-2, NF-κB. significantly increases plasma BDNF, factor, plasticity, activity, memory, exploratory behavior subjects. Irisin myokine released from skeletal muscle during protects hippocampus by suppressing Aβ accumulation promoting proliferation STAT3 signaling. Therefore, combined strength balance coordination social activities seems provide important benefits for people

Язык: Английский

---

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Март 6, 2024

Abstract Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes response specific microenvironmental signals. Our latest vivo vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival axonal outgrowth, transplantation of aOECs improves neurological outcome after spinal cord (SCI). The therapeutic effect is largely attributed aOEC activity through modulation microglial polarization from M1 M2 phenotype. However, very little known about what viable molecules actively responsible for switch underlying mechanisms polarization. Herein, we show Interleukin-4 (IL-4) plays a leading role triggering phenotype, appreciably decreasing levels markers IL‑1β, IL‑6, tumour necrosis factor-alpha (TNF-α) inducible nitric oxide synthase (iNOS) elevating Arg-1, TGF-β, IL-10, CD206. Strikingly, blockade IL-4 signaling by siRNA neutralizing antibody medium reverses transition M2, activated microglia stimulated with lacking significantly decreases neuronal neurite outgrowth. In addition, improved function deficits SCI rats. More importantly, crosstalk between JAK1/STAT1/3/6-targeted downstream signals NF-κB/SOCS1/3 predominantly orchestrates IL-4-modulated event. These results provide new insights into molecular driving M1-to-M2 shift shed light on therapies

Язык: Английский

---

Nrf2 Suppresses Oxidative Stress and Inflammation inAppKnock-In Alzheimer’s Disease Model Mice

Molecular and Cellular Biology, Год журнала: 2020, Номер 40(6)

Опубликована: Янв. 9, 2020

Nrf2 (NF-E2-related-factor 2) is a stress-responsive transcription factor that protects cells against oxidative stresses. To clarify whether prevents Alzheimer's disease (AD), AD model AppNL-G-F/NL-G-F knock-in (AppNLGF) mice were studied in combination with genetic induction Keap1FA/FA mice. While AppNLGF displayed shorter latency to escape than wild-type the passive-avoidance task, impairment was improved AppNLGF::Keap1FA/FA Matrix-assisted laser desorption ionization–mass spectrometry imaging revealed reduced glutathione levels elevated by mouse brains compared brains. Genetic markedly suppressed elevation of stress marker 8-OHdG and Iba1-positive microglial cell number. We also determined plasmalogen-phosphatidylethanolamine (PlsPE) level as an biomarker. PlsPE containing polyunsaturated fatty acids decreased brain, but attenuated this decline. evaluate pharmacological elicits beneficial effects for treatment, we tested natural compound 6-MSITC [6-(methylsulfinyl)hexyl isothiocyanate]. Administration impaired cognition task. These results demonstrate ameliorates cognitive suppressing neuroinflammation, suggesting important therapeutic target AD.

Язык: Английский

---

Sialylation and Galectin-3 in Microglia-Mediated Neuroinflammation and Neurodegeneration

Frontiers in Cellular Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Июнь 9, 2020

Microglia are brain macrophages that mediate neuroinflammation and contribute to protect against neurodegeneration. The terminal sugar residue of all glycoproteins glycolipids on the surface mammalian cells is normally sialic acid, addition this negatively charged known as "sialylation," whereas removal by sialidases "desialylation." High sialylation neuronal cell inhibits microglial phagocytosis such neurons, via: (i) activating acid receptors (Siglecs) microglia inhibit (ii) inhibiting binding opsonins C1q, C3, galectin-3. Microglial inflammatory activation Siglec CD22 CD33 Toll-like receptor 4 (TLR4), complement 3 (CR3), other receptors. When activated, release a sialidase activity desialylates both rendering neurons susceptible phagocytosis. Activated also galectin-3 (Gal-3), which: further activates via TLR4 TREM2, binds desialylated opsonizing them for Mer tyrosine kinase, (iii) promotes Aβ aggregation toxicity in vivo. Gal-3 desialylation may increase variety pathologies. Thus, potential treatment targets prevent

Язык: Английский

---

An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events

Antioxidants, Год журнала: 2020, Номер 9(3), С. 216 - 216

Опубликована: Март 5, 2020

The inflammation process represents of a dynamic series phenomena that manifest themselves with an intense vascular reaction. Neuroinflammation is reply from the central nervous system (CNS) and peripheral (PNS) to changed homeostasis. There are two cell systems mediate this process: glia CNS lymphocites, monocytes, macrophages hematopoietic system. In both systems, neuroinflammation plays important role in pathogenesis neurodegenerative diseases, such as Parkinson’s Alzheimer’s neuropsychiatric illnesses, depression autism spectrum disorders. resolution allows for inflamed tissues return players represented by lipid mediators. Among naturally occurring signaling molecules, prominent played N-acylethanolamines, namely N-arachidonoylethanolamine its congener N-palmitoylethanolamine, which also named palmitoylethanolamide or PEA. PEA possesses powerful neuroprotective anti-inflammatory power but has no antioxidant effects per se. For reason, co-ultramicronization flavonoid luteolin more efficacious than either molecule alone. Inhibiting modulating enzymatic breakdown complementary therapeutic approach treating neuroinflammation. aim review discuss ultramicronized co-ultramicronized several neurological diseases using preclinical clinical approaches.

Язык: Английский

---

Contribution of astrocytes to neuropathology of neurodegenerative diseases

Brain Research, Год журнала: 2021, Номер 1758, С. 147291 - 147291

Опубликована: Янв. 28, 2021

Язык: Английский

---