Cerebral endothelial cell-derived extracellular vesicles regulate microglial polarization and promote autophagy via delivery of miR-672-5p DOI Creative Commons
Changshui Wang, Lei Feng, Li Zhu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 29, 2023

The interaction between cerebral endothelial cells (CEC) and brain parenchymal is critical to maintain neurovascular homeostasis, whereas extracellular vesicles (EVs) are essential mediate the cell-cell communication. Previous researches demonstrated that CEC-derived EVs (CEC-EVs) confer neuroprotective actions. However, molecular mechanisms remain unknown. In this study, we isolated from CEC assessed their immune-regulatory actions in microglial mice following lipopolysaccharide (LPS) exposure. We found CEC-EVs treatment significantly ameliorated LPS-induced inflammatory activation, shifting polarization pro-inflammatory phenotype anti-inflammatory phenotype. Meanwhile, can effectively internalize process was further enhanced by immune activation. Next, miRNA microarray analysis revealed increased expression of miR-672-5p, which be cargo CEC-EVs. TGFβ-activated kinase 1 (TAK1)-binding proteins 2 (TAB2) identified target miR-672-5p. Through inhibiting TAB2, miR-672-5p derived suppressed TAK1-TAB signaling thereby mitigating downstream NF-κB Furthermore, delivering promoted autophagy hence stimulating autophagic degradation NLRP3 inflammasome. Our work firstly neuroimmune-modulating secreted inhibits facilitates via targeting TAB2.

Language: Английский

Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson’s disease DOI

Qiankun Lv,

Kang‐Xin Tao,

Xiaobo Wang

et al.

Inflammation Research, Journal Year: 2023, Volume and Issue: 72(3), P. 443 - 462

Published: Jan. 4, 2023

Language: Английский

Citations

54
The Multiple Roles of Autophagy in Neural Function and Diseases DOI Creative Commons
Yanyan Li,

Zheng‐Hong Qin,

Rui Sheng

et al.

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(3), P. 363 - 382

Published: Oct. 19, 2023

Abstract Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, organelles are degraded recycled. According way components engulfed, autophagy can be divided into macroautophagy, microautophagy, chaperone-mediated autophagy. Recently, many studies have found that plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's Huntington's neuronal excitotoxicity, cerebral ischemia. maintains cell homeostasis nervous system via degradation misfolded elimination damaged organelles, regulation apoptosis inflammation. AMPK-mTOR, Beclin 1, TP53 , endoplasmic reticulum stress, other signal pathways involved used as potential therapeutic targets for diseases. Here, we discuss role, functions, which will shed light on pathogenic mechanisms diseases suggest novel therapies.

Language: Английский

Citations

48
A peptide from Boletus griseus‐Hypomyces chrysospermus protects against hypertension and associated cardiac and renal damage through modulating RAAS and intestinal microbiota DOI Open Access

Pengtao Huan,

Liping Sun, Shupeng Chen

et al.

Journal of Food Science, Journal Year: 2025, Volume and Issue: 90(1)

Published: Jan. 1, 2025

Abstract Hypertension is a major risk factor for many cardiovascular diseases, which can lead to kidney and heart disease, stroke, premature death. Inhibiting angiotensin‐converting enzyme (ACE) activity an effective method relieve hypertension. Previously, we screened active peptide KYPHVF (KF6) from Boletus griseus‐Hypomyces chrysospermus with excellent ACE inhibitory activity. This study further evaluated the antihypertensive of KF6 in vivo. at 10 mg/kg Captopril (CAP, positive control) were administrated spontaneous hypertensive rats (SHRs) 5 weeks. The results demonstrated that effectively lowered both diastolic blood pressure (DBP) systolic (SBP), decreased ACE, AGT, ALD, ANG II levels serum SHRs. Furthermore, cardiac renal injury SHRs ameliorated by through inhibiting fibrosis, inflammation, oxidative stress. Moreover, inhibited ACE‐ANG II‐AT1 axis while activating ACE2‐Ang (1‐7)‐MAS1L pathway, two mutually antagonistic axes RAAS, Additionally, improved intestinal microbiota composition, mainly increasing abundance Prevotella Phascolarctobacterium decreasing Alistipes , Clostridium_IV Nosocomiicoccus Allobaculum . Overall, promising lowering mitigating hypertension‐related damage. protective effect against hypertension attributed its ability modulate RAAS microbiota.

Language: Английский

Citations

2
The GLP-1 Agonist Semaglutide Ameliorates Cognitive Regression in P301S Tauopathy Mice Model via Autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization DOI
Norhan N. Elbadawy, Muhammed A. Saad, Sara Elfarrash

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177305 - 177305

Published: Jan. 1, 2025

Language: Английский

Citations

2
Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy DOI Creative Commons
Xuefei Fu,

Shuyu Feng,

Huan Qin

et al.

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

Published: Jan. 23, 2023

Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during development. In certain diseases, activated microglia promote hypoxia stress through neurovascular coupling guide neovascularization to avascular areas (e.g., outer nuclear layer macula lutea). Furthermore, continuously secrete inflammatory factors expedite loss of blood-retinal barrier which causes irreversible damage secondary death neurons. this review, we support can be a potential cellular therapeutic target retinopathy. We briefly describe relevance vasculature barrier. Then discuss signaling pathway related how move their destinations regulate vascular regeneration. summarize properties different disease models propose reducing number pro-inflammatory microglial conversing phenotypes from anti-inflammatory feasible for treating damaged (BRB). Finally, suppose unique may aid vascularization organoids.

Language: Английский

Citations

30
Phosphoproteomics for studying signaling pathways evoked by hormones of the renin‐angiotensin system: A source of untapped potential DOI Creative Commons
Igor Maciel Souza‐Silva, Victor Corasolla Carregari, U. Muscha Steckelings

et al.

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 16, 2025

The Renin-Angiotensin System (RAS) is a complex neuroendocrine system consisting of single precursor protein, angiotensinogen (AGT), which processed into various peptide hormones, including the angiotensins [Ang I, Ang II, III, IV, Ang-(1-9), Ang-(1-7), Ang-(1-5), etc] and Alamandine-related peptides A, Alamandine, Ala-(1-5)], through intricate enzymatic pathways. Functionally, RAS divided two axes with opposing effects: classical axis, primarily II acting AT1 receptor (AT1R), in contrast protective includes receptors Mas, AT2R MrgD their respective ligands. A key area research to gain better understanding how signaling cascades elicited by these lead either "classical" or "protective" effects, as imbalances between can contribute disease. On other hand, therapeutic benefits be achieved selectively activating associated Traditionally, robust "hypothesis-driven" methods like Western blotting have built solid knowledge foundation on signaling. In this review, we introduce untargeted mass spectrometry-based phosphoproteomics, "hypothesis-generating approach", explore This technology enables unbiased discovery phosphorylation events, offering insights previously unknown mechanisms. We review existing studies used phosphoproteomics study discuss potential future applications advantages limitations. Ultimately, represents so far underused tool for deepening our unveiling novel targets.

Language: Английский

Citations

1
Activation of angiotensin‐converting enzyme 2/angiotensin (1–7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling DOI Creative Commons
Ruili Dang, Mengqi Yang, Changmeng Cui

et al.

Aging Cell, Journal Year: 2021, Volume and Issue: 20(10)

Published: Sept. 16, 2021

Brain renin-angiotensin (Ang) system (RAS) is implicated in neuroinflammation, a major characteristic of aging process. Angiotensin II, produced by angiotensin-converting enzyme (ACE), activates immune via angiotensin type 1 receptor (AT1), whereas Ang(1-7), generated ACE2, binds with Mas (MasR) to restrain excessive inflammatory response. Therefore, the present study aims explore relationship between RAS and neuroinflammation. We found that repeated lipopolysaccharide (LPS) treatment shifted balance ACE/Ang II/AT1 ACE2/Ang(1-7)/MasR axis deleterious side either MasR agonist, AVE0991 (AVE) or ACE2 activator, diminazene aceturate, exhibited strong neuroprotective actions. Mechanically, activation triggered Forkhead box class O1 (FOXO1)-autophagy pathway induced superoxide dismutase (SOD) catalase (CAT), FOXO1-targeted antioxidant enzymes. Meanwhile, knockdown FOXO1 BV2 cells, using selective inhibitor, AS1842856, animals, suppressed translocation compromised autophagic process activation. further used chloroquine (CQ) block autophagy showed suppressing abrogated anti-inflammatory action AVE. Likewise, Ang(1-7) also signaling flux following LPS cells. Cotreatment AS1842856 CQ all led inhibition thereby abolished Ang(1-7)-induced remission on NLRP3 inflammasome caused exposure, shifting microglial polarization from M1 M2 phenotype. Collectively, these results firstly illustrated mechanism strongly indicating involvement FOXO1-mediated neuroimmune-modulating effects

Language: Английский

Citations

45
Role of brain renin–angiotensin system in depression: A new perspective DOI Creative Commons

Naif H. Ali,

Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(4)

Published: Nov. 12, 2023

Abstract Depression is a mood disorder characterized by abnormal thoughts. The pathophysiology of depression related to the deficiency serotonin (5HT), which derived from tryptophan (Trp). Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in pathogenesis depression. Notably, renin–angiotensin system (RAS) depression, different findings revealed that angiotensin‐converting enzyme inhibitors (ACEIs) angiotensin receptor blockers (ARBs) may be effective However, underlying mechanism for role dysregulated brain RAS‐induced remains speculative. Therefore, this review aimed revise conceivable ACEIs ARBs how these agents ameliorate Dysregulation RAS triggers development progression through reduction 5HT expression brain‐derived neurotrophic factor (BDNF) induction mitochondrial neuroinflammation. inhibition central classical ARBS activation non‐classical prevent regulating 5HT, BDNF,

Language: Английский

Citations

19
A Triple-Targeted Rutin-Based Self-Assembled Delivery Vector for Treating Ischemic Stroke by Vascular Normalization and Anti-Inflammation via ACE2/Ang1-7 Signaling DOI Creative Commons

Tingkui Zhao,

Fujin He,

Ke‐Qing Zhao

et al.

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(6), P. 1180 - 1199

Published: June 5, 2023

Changes in the cerebral microenvironment caused by acute ischemic stroke-reperfusion are main obstacle to recovery of neurological function and an important cause stroke recurrence after thrombolytic therapy. The intracerebral ischemia-reperfusion reduces neuroplasticity penumbra ultimately leads permanent damage. To overcome this challenge, we developed a triple-targeted self-assembled nanodelivery system, which combines neuroprotective drug rutin with hyaluronic acid through esterification form conjugate, then connected SS-31, small peptide that can penetrate blood brain barrier target mitochondria. Brain targeting, CD44-mediated endocytosis, hyaluronidase 1-mediated degradation, acidic environment synergistically promoted enrichment nanoparticles release injured area. Results demonstrate has high affinity for ACE2 receptors on cell membrane directly activate ACE2/Ang1-7 signaling, maintain neuroinflammation, promote angiogenesis normal neovascularization. Importantly, delivery system enhanced overall plasticity area significantly reduced damage stroke. relevant mechanism was expounded from aspects behavior, histology, molecular cytology. All results suggest our may be effective safe strategy treatment injury.

Language: Английский

Citations

18
ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway DOI
Ya Li,

Tiantian Wan,

Jiaxin Li

et al.

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

Published: March 27, 2024

Language: Английский

Citations

7