Neuroprotective and anti‐inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies

Phytotherapy Research, Год журнала: 2024, Номер 38(6), С. 3169 - 3189

Опубликована: Апрель 14, 2024

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid‐beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, polyphenolic compound derived from Curcuma longa , has shown potential neuroprotective effects due its anti‐inflammatory antioxidant properties. This review aims synthesize current preclinical data on anti‐neuroinflammatory mechanisms curcumin in context AD, addressing pharmacokinetics, bioavailability, as therapeutic adjunct. An exhaustive literature search was conducted, focusing recent studies within last 10 years related curcumin's impact neuroinflammation role AD. The methodology included sourcing articles specialized databases using specific medical subject headings terms ensure precision relevance. Curcumin demonstrates significant properties modulating neuroinflammatory pathways, scavenging reactive oxygen species, inhibiting production pro‐inflammatory cytokines. Despite potential, challenges remain regarding limited bioavailability scarcity comprehensive human clinical trials. emerges promising adjunct AD multimodal benefits. However, further research required overcome establish effective dosing regimens subjects. Developing novel delivery systems formulations may enhance treatment.

Язык: Английский

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Fully bioresorbable hybrid opto-electronic neural implant system for simultaneous electrophysiological recording and optogenetic stimulation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 6, 2024

Abstract Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges secondary surgeries for removal implanted devices required existing implants. In this study, we introduce fully bioresorbable flexible hybrid opto-electronic system simultaneous electrophysiological recording and optogenetic stimulation. The soft device, composed materials, has direct optical electrical interface with curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized minimize light transmission losses photoelectric artifact interference, device was chronically in brain transgenic mice performed photo-stimulate somatosensory area local field potentials. Thus, presented implant system, comprising promises provide monitoring therapy modalities versatile applications biomedicine.

Язык: Английский

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Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Июль 23, 2024

Abstract Background Astrocytes, one of the most resilient cells in brain, transform into reactive astrocytes response to toxic proteins such as amyloid beta (Aβ) Alzheimer’s disease (AD). However, astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study find out whether Aβ-induced proteotoxic stress affects expression autophagy genes and modulation autophagic flux astrocytes, if yes, how autophagy-associated are involved Aβ clearance animal model AD. Methods Whole RNA sequencing (RNA-seq) was performed detect gene patterns Aβ-treated human a time-dependent manner. To verify role astrocytic an AD mouse model, we developed AAVs expressing shRNAs for MAP1LC3B/LC3B (LC3B) Sequestosome1 ( SQSTM1) based on AAV-R-CREon vector, which Cre recombinase-dependent gene-silencing system. Also, effect astrocyte-specific overexpression LC3B neuropathology (APP/PS1) mice determined. Neuropathological alterations with dysfunction were observed by confocal microscopy transmission electron microscope (TEM). Behavioral changes examined through novel object recognition test (NOR) place (NOPR). Results Here, show that unlike neurons, undergo plastic processes remove Aβ. transiently induces turns prolonged transcription SQSTM1 gene. The accelerates urea cycle putrescine degradation pathway. Pharmacological inhibition exacerbates mitochondrial oxidative astrocytes. Astrocyte-specific knockdown significantly increases plaque formation GFAP-positive APP/PS1 mice, along significant reduction neuronal marker cognitive function. In contrast, reduced aggregates brain mice. An increase protein found hippocampus patients. Conclusions Taken together, data indicates plasticity important cellular event modulate maintain function

Язык: Английский

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Phytomedicine for neurodegenerative diseases: The road ahead

Phytotherapy Research, Год журнала: 2024, Номер 38(6), С. 2993 - 3019

Опубликована: Апрель 10, 2024

Abstract Neurodegenerative disorders (NDs) are among the most common causes of death across globe. NDs characterized by progressive damage to CNS neurons, leading defects in specific brain functions such as memory, cognition, and movement. The Parkinson's, Alzheimer's, Huntington's, amyotrophic lateral sclerosis (ALS). Despite extensive research, no therapeutics or medications against have been proven be effective. current treatment involving symptom‐based targeting disease pathogenesis has certain limitations, drug resistance, adverse side effects, poor blood–brain barrier permeability, bioavailability drugs. Some studies shown that plant‐derived natural compounds hold tremendous promise for treating preventing NDs. Therefore, primary objective this review article is critically analyze properties potency some studied phytomedicines, quercetin, curcumin, epigallocatechin gallate (EGCG), apigenin, cannabinoids, highlight their advantages limitations developing next‐generation alternative treatments Further research on pre‐clinical clinical plant‐based drugs from bench bedside warranted.

Язык: Английский

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SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 15, 2025

Abstract Background Alzheimer’s Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and H 2 O are associated memory impairment in AD synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, enzymes downstream to MAOB this pathway remain unidentified. Methods Using transcriptomics analysis, we identified two candidate enzymes, Aldehyde Dehydrogenase 1 family member A1 (ALDH1A1) Sirtuin (SIRT2) for steps following production pathway. We used immunostaining, metabolite analysis electrophysiology, both vitro vivo, confirm participation these production. checked presence SIRT2 human patients as well mouse model APP/PS1 finally, selectively ablated astrocytes mice observe its effects on pathology. Results Immunostaining, electrophysiology recapitulated ALDH1A1 Inhibition reduced but not , key molecule neurodegeneration. Elevated expression was found hippocampal mice. Astrocyte-specific gene-silencing restored partially improved function. Conclusions Our study first identify specific role reactive astrogliosis determine metabolic step catalyzed by enzyme. partial, yet significant process, thereby highlighting new players findings therefore, offer tool segregate from production, aiding future research diseases. Graphical

Язык: Английский

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Relationship Between Reactive Astrocytes, by [18F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer’s Disease

Molecular Neurobiology, Год журнала: 2024, Номер 61(10), С. 8387 - 8401

Опубликована: Март 19, 2024

Reactive astrocytes play an important role in the development of Alzheimer's disease (AD). Here, we aimed to investigate temporospatial relationships among monoamine oxidase-B, tau and amyloid-β (Aβ), translocator protein, glucose metabolism by using multitracer imaging AD transgenic mouse models. Positron emission tomography (PET) with [

Язык: Английский

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Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma

Nuclear Medicine and Molecular Imaging, Год журнала: 2024, Номер 58(4), С. 237 - 245

Опубликована: Фев. 21, 2024

Positron emission tomography/computed tomography (PET/CT) has dramatically altered the landscape of noninvasive glioma evaluation, offering complementary insights to those gained through magnetic resonance imaging (MRI). PET/CT scans enable a multifaceted analysis biology, supporting clinical applications from grading and differential diagnosis mapping full extent tumors planning subsequent treatments evaluations. With broad array specialized radiotracers, researchers clinicians can now probe various biological characteristics gliomas, such as glucose utilization, cellular proliferation, oxygen deficiency, amino acid trafficking, reactive astrogliosis. This review aims provide recent update on application versatile radiotracers in research practice.

Язык: Английский

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Identification of therapeutic targets for Alzheimer’s Disease Treatment using bioinformatics and machine learning

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 31, 2025

Alzheimer's disease (AD) is a complex neurodegenerative disorder that currently lacks effective treatment options. This study aimed to identify potential therapeutic targets for the of AD using comprehensive bioinformatics methods and machine learning algorithms. By integrating differential gene expression analysis, weighted co-expression network Mfuzz clustering, single-cell RNA sequencing, algorithms including LASSO regression, SVM-RFE, random forest, five hub genes related AD, PLCB1, NDUFAB1, KRAS, ATP2A2, CALM3 were identified. in particular, exhibited highest diagnostic value showed significant correlation with Braak stages neuronal expression. Furthermore, Noscapine, PX-316, TAK-901 selected as drugs based on PLCB1. research provides reliable method discovery construction models, offering important insights directions future strategies drug development.

Язык: Английский

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Tonic excitation by astrocytic GABA causes neuropathic pain by augmenting neuronal activity and glucose metabolism

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(5), С. 1193 - 1205

Опубликована: Май 17, 2024

Abstract Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and often characterized allodynia. Although neuron-independent mechanisms have been investigated, contribution astrocyte-neuron interactions remains unclear. Here, we show evidence reactive astrocytes their excessive GABA release in horn, which paradoxically leads to tonic excitation neighboring neuropathic model. Using multiple electrophysiological methods, demonstrated that neuronal attributed both increased astrocytic synthesis via monoamine oxidase B (MAOB) depolarized reversal potential GABA-mediated currents (E ) downregulation K + /Cl − cotransporter KCC2. Furthermore, longitudinal 2-deoxy-2-[ 18 F]-fluoro-D-glucose microPET imaging regional glucose metabolism ipsilateral reflecting hyperexcitability. Importantly, inhibiting MAOB restored entire cascade abrogated mechanical Overall, critical for hyperexcitability, leading allodynia pain.

Язык: Английский

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Mechanism of Ginkgo Diterpene Lactone Meglumine Injection Promoting Angiogenesis and Improving Cerebral Perfusion in Cerebral Infarction Rats

Pharmacognosy Magazine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Background In recent years, traditional Chinese medicine has shown advantages in treating ischemic cerebrovascular diseases, including multi-component, multi-target, and low toxicity effects. Purpose: The aim of this study was to clarify the impact ginkgo diterpene lactone meglumine injection (GDLMI) on promoting microvascular neovascularization improving cerebral perfusion after infarction (CIF) rats explore its underlying mechanisms angiogenesis. Methods Seventy-five were randomly rolled into Sham (sham surgery) group, Model (acute CIF model) low-dose (LD) (1 g/kg bw GDLMI) medium-dose (MD) (3 high-dose (HD) (5 group. neurological function evaluated using Longa method. Micro-PET performed evaluate brain metabolism status at 7 days post-reperfusion. Serum expression levels (ELs) interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α measured. Brain tissue samples collected assess infarct volume measure oxidative stress (OS) markers, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA). TdT-mediated dUTP nick end labeling (TUNEL) detect apoptosis rate cortical neurons. Western blotting conducted determine tissue’s ELs vascular endothelial growth (VEGF), angiopoietins-1 (Ang-1), p-PI3K, p-AKT proteins. Results Rats group exhibited higher scores increased volume, decreased 18 F-FDG content, elevated serum IL-1β, TNF-α, reduced SOD CAT activities, MDA content tissue, neurons, protein VEGF Ang-1 accompanied by p-PI3K proteins compared ( p < 0.05). LD, MD, HD groups showed VEGF, Ang-1, versus effects all indicators a dose-dependent trend. Conclusion GDLMI protective effect against acute CIF/reperfusion injury (RI), which may be attributed ability suppress inflammation OS damage activating PI3K/AKT signaling.

Язык: Английский

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