Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson’s Disease Intervention DOI Creative Commons

Fangfang Ban,

Longjian Zhou, Zhiyou Yang

et al.

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(5), P. 181 - 181

Published: April 23, 2025

Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from Aspergillus unguis DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP+)-induced primary cortical neurons anti-neuroinflammatory property, promising be potential agent Parkinson’s disease (PD). To further explore the anti-PD mechanisms of Asp G, we employed network pharmacology, cellular experiments, various biological techniques analysis validation. The pharmacology suggested that G’s might attributed its modulation inflammation. data nitric oxide (NO) detection, qRT-PCR, Western blot confirmed dose-dependently inhibited lipopolysaccharide (LPS)-stimulated NO production, with 40 μM suppressing 90.54% burst compared LPS group, suppressed overproduction inflammatory-related factors in LPS-induced BV2 cells. Further protein–protein interaction indicated matrix metalloproteinase 9 (MMP9), target PD intervention, was most likely results gelatin zymography, validated could inhibit active inactive forms MMP9 directly indirectly, respectively. Notably, inhibition 67 kDa-MMP9 by is expected compensate inability TIMP-1 this form. Furthermore, selective inhibitor (20 SB-3CT) potentiated anti-inflammatory effects μM), rate on increasing 27.57% 63.50% group. In summary, our revealed exerts inhibiting MMP9, provides valuable lead compound development drugs offers insights into intervention PD-associated neuroinflammation. Future studies will investigate upstream regulatory G-mediated vivo models.

Language: Английский

Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration DOI Creative Commons
Stanisław Szlufik,

Kamila Kopeć,

Stanisław Szleszkowski

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 286 - 286

Published: Feb. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Language: Английский

Citations

16
New perspectives on the glymphatic system and the relationship between glymphatic system and neurodegenerative diseases DOI Creative Commons
Yujie Sun,

Qiankun Lv,

Junyi Liu

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: 205, P. 106791 - 106791

Published: Jan. 6, 2025

Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial (ISF), facilitates movement metabolic substances within brain, serving functions akin to those peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on removal pathological in ND. article elucidates recent discoveries regarding system updates relevant concepts model. It discusses potential roles ND, including Alzheimer's disease (AD), Parkinson's (PD), multiple atrophy (MSA), proposes as therapeutic target for these conditions.

Language: Английский

Citations

2
The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross‐Sectional Studies DOI

Peikun He,

Lin Shi, Yanyi Li

et al.

Annals of Neurology, Journal Year: 2023, Volume and Issue: 94(4), P. 672 - 683

Published: June 28, 2023

Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, clinical this remains lacking.In study, index for diffusion tensor image analysis along perivascular space (ALPS index) was calculated to evaluate function.Overall, 289 patients with PD were enrolled in cross-sectional study. The ALPS found be negatively correlated age, severity, dyskinesia. In longitudinal information on a total 95 5-year follow-up examinations collected from Progression Marker Initiative, 33 which classified into low group, all others mid-high group based first tertile baseline index. results regression indicated significant main effect autonomic dysfunction, as well activities daily living. addition, had faster deterioration MDS-UPDRS part III II, Symbol Digit Modalities Test Hopkins Verbal Learning Test. Path showed acted mediator tTau/ Aβ1-42 cognitive change score at year 4 5.The index, neuroimaging marker function, motor symptoms, predictive symptoms function. Additionally, function may mediate role toxic protein decline. ANN NEUROL 2023;94:672-683.

Language: Английский

Citations

25
Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage DOI Creative Commons
Junbo Liao,

Yingxing Duan,

Yaxue Liu

et al.

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 216, P. 111045 - 111045

Published: Aug. 5, 2024

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution acute phase ICH, though precise mechanisms remain unclear. Recent findings have highlighted glymphatic system (GS) as a crucial component intracranial cerebrospinal fluid circulation, playing significant role clearance post-ICH. This study investigates link between SIM efficacy GS. Our experimental results show alleviates GS damage ICH-induced rats, resulting improved outcomes such reduced brain edema, neuronal apoptosis, degeneration. Further analysis reveals SIM's effects are mediated through VEGF-C/VEGFR3/PI3K-Akt pathway. advances our understanding mechanism promoting underscores potential targeting for ICH treatment.

Language: Английский

Citations

12
Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease DOI Creative Commons
Wen Wu,

Yubai Zhao,

Xin R. Cheng

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms treatments remain elusive. Here we report therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model disease. Our findings reveal that treatment prevents memory decline 4-month-old mice motivation loss 14-month-old mice, accompanied restoration glial water channel aquaporin-4 polarity, improved brain drainage efficiency, reduction hippocampal lipid accumulation. We further demonstrate beneficial effects are mediated through activation vLGN/IGL-Re visual circuit. Notably, concomitant use anti-Aβ antibody with demonstrates soluble Aβ clearance performance mice. These offer functional evidence on Aβ-related pathologies suggest its as supplementary strategy to augment efficacy antibody-based therapy. Treatments for (AD) limited. Here, authors show activates circuit boost glymphatic drainage, enhances memory, motivation, therapy AD.

Language: Английский

Citations

1
Aquaporin-4 and Parkinson’s Disease DOI Open Access
К. В. Лапшина, И. В. Екимова

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1672 - 1672

Published: Jan. 30, 2024

The water-selective channel aquaporin-4 (AQP4) is implicated in water homeostasis and the functioning of glymphatic system, which eliminates various metabolites from brain tissue, including amyloidogenic proteins. Misfolding α-synuclein protein its post-translational modifications play a crucial role development Parkinson’s disease (PD) other synucleopathies, leading to formation cytotoxic oligomers aggregates that cause neurodegeneration. Human animal studies have shown an interconnection between AQP4 dysfunction accumulation; however, specific these mechanisms remains unclear. This review summarizes current knowledge on progression pathology, considering possible effects dysregulation molecular can impact modification, accumulation aggregation. It also highlights future directions help study protective during PD neurodegenerative diseases.

Language: Английский

Citations

7
Ginkgolide B can alleviate spinal cord glymphatic system dysfunction and provide neuroprotection in painful diabetic neuropathy rats by inhibiting matrix metalloproteinase-9 DOI
Jiang Li, Shuaiying Jia,

Yuehan Song

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 250, P. 109907 - 109907

Published: March 14, 2024

Language: Английский

Citations

7
Resveratrol differentially affects MMP‐9 release from neurons and glia; implications for therapeutic efficacy DOI Creative Commons
Matthew Amontree, Matthew N. Nelson,

Lara Stefansson

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Abstract Resveratrol, a naturally occurring polyphenol that activates sirtuin 1 (SIRT1), has been shown to reduce overall levels of matrix metalloprotease‐9 (MMP‐9) in cerebrospinal fluid (CSF) samples from patients with Alzheimer's dementia (AD). Depending on the site release, however, MMP‐9 potential improve or impair cognition. In particular, its release microglia pericytes proximal blood brain barrier can damage basement membrane, while neuronal activity‐dependent this protease glutamatergic neurons instead promote dendritic spine expansion and long‐term potentiation synaptic plasticity. present study, we test hypothesis resveratrol reduces CSF APOE4, an allele associated increased glial inflammation. We also examine possibility inflammation‐associated MMP cultured glia but spares cortical neurons. observe decreases MMP‐2 AD patients. Resveratrol tissue inhibitor metalloproteinases‐1 (TIMP‐1), glial‐derived protein restricts transmission, individuals homozygous for APOE4. Consistent these results, basal lipopolysaccharide (LPS)‐stimulated TIMP‐1 astrocytes. contrast, does not inhibit Overall, results are consistent potentially maladaptive activated glia, neuroplasticity‐promoting is spared. neurocan brevican, extracellular components restrict neuroplasticity, both glia. These data underscore diversity resveratrol's actions respect affected cell types molecular targets suggest further studies may be warranted determine if effects could make it useful adjunct AD‐ and/or anti‐amyloid therapy‐related barrier.

Language: Английский

Citations

6
Dystrophin 71 deficiency causes impaired aquaporin-4 polarization contributing to glymphatic dysfunction and brain edema in cerebral ischemia DOI Creative Commons
Jian Yang, Chang Cao, Jiale Liu

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 199, P. 106586 - 106586

Published: June 29, 2024

Language: Английский

Citations

6
Dexmedetomidine improves the circulatory dysfunction of the glymphatic system induced by sevoflurane through the PI3K/AKT/ΔFosB/AQP4 pathway in young mice DOI Creative Commons
Shuying Wang, Xiaojin Yu,

Lili Cheng

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 25, 2024

Abstract Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, effect on glymphatic system not clearly studied. We hypothesized that could alleviate sevoflurane-induced circulatory dysfunction young mice. Six-day-old C57BL/6 mice were exposed to 3% for 2 h daily, continuously 3 days. Intraperitoneal injection either normal saline or was administered before every anaesthesia. Meanwhile detected by tracer at P8 P32. On P30-P32, behavior tests including open field test, novel object recognition Y-maze test conducted. Primary astrocyte cultures established treated with PI3K activator 740Y-P, dexmedetomidine, small interfering RNA (siRNA) silence ΔFosB. propose first time multiple exposure induces Dexmedetomidine improves capacity following repeated through PI3K/AKT/ΔFosB/AQP4 signaling pathway, enhances their long-term learning working memory abilities.

Language: Английский

Citations

5