Regulation of blood–brain barrier integrity by microglia in health and disease: A therapeutic opportunity

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2020, Volume and Issue: 40(1_suppl), P. S6 - S24

Published: Sept. 14, 2020

The blood–brain barrier (BBB) is a critical regulator of CNS homeostasis. It possesses physical and biochemical characteristics (i.e. tight junction protein complexes, transporters) that are necessary for the BBB to perform this physiological role. Microvascular endothelial cells require support from astrocytes, pericytes, microglia, neurons, constituents extracellular matrix. This intricate relationship implies existence neurovascular unit (NVU). NVU cellular components can be activated in disease contribute dynamic remodeling BBB. especially true resident immune brain, which polarize into distinct proinflammatory (M1) or anti-inflammatory (M2) phenotypes. Current data indicate M1 pro-inflammatory microglia dysfunction vascular “leak”, while M2 play protective role at Understanding biological mechanisms involved activation provides unique opportunity develop novel treatment approaches neurological diseases. In review, we highlight describe how these phenotypes modulate physiology. Additionally, outline other cell types regulating microglial targeted with focus on ischemic stroke Alzheimer’s disease.

Language: Английский

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Novel Therapeutic Approaches for Alzheimer’s Disease: An Updated Review

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 8208 - 8208

Published: July 30, 2021

Alzheimer's disease (AD) is a progressive neurodegenerative and accounts for most cases of dementia. The prevalence AD has increased in the current rapidly aging society contributes to heavy burden on families society. Despite profound impact AD, treatments are unable achieve satisfactory therapeutic effects or stop progression disease. Finding novel become urgent. In this paper, we reviewed approaches five categories: anti-amyloid therapy, anti-tau anti-neuroinflammatory neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, brain stimulation. trend development shifting from single pathological target more complex mechanism, such as neuroinflammatory processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) direct (tDCS), also have potential clinical application. future, it possible physicians choose appropriate interventions individually basis precision medicine.

Language: Английский

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Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 371 - 371

Published: Feb. 25, 2022

Alzheimer’s and Parkinson’s diseases are the two most common forms of neurodegenerative diseases. The exact etiology these disorders is not well known; however, environmental, molecular, genetic influences play a major role in pathogenesis Using disease (AD) as archetype, pathological findings include aggregation Amyloid Beta (Aβ) peptides, mitochondrial dysfunction, synaptic degradation caused by inflammation, elevated reactive oxygen species (ROS), cerebrovascular dysregulation. This review highlights neuroinflammatory neuroprotective epigallocatechin-3-gallate (EGCG): medicinal component green tea, known nutraceutical that has shown promise modulating AD progression due to its antioxidant, anti-inflammatory, anti-aging abilities. report also re-examines current literature provides innovative approaches for EGCG be used preventive measure alleviate other disorders.

Language: Английский

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Role of Nrf2 in aging, Alzheimer’s and other neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 82, P. 101756 - 101756

Published: Oct. 13, 2022

Language: Английский

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Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: From chemistry to medicine

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115215 - 115215

Published: July 24, 2023

Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction the nervous system. Some common NDDs include Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding pathological mechanisms recent years, development targeted effective drugs for their treatment remains challenging. Kaempferol is flavonoid whose derivatives kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, kaempferide. Emerging studies have suggested kaempferol its possess neuroprotective properties may potential therapeutic benefits NDDs. Here, we aimed to provide theoretical basis use clinical We systematically reviewed literature PubMed, Web Science, Science Direct databases until June 2022 using search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," "biosynthesis" according reporting items systematic review (PRISMA) standard. Based on combined results vivo vitro studies, summarize basic targets management AD, PD, HD, ALS. exert role mainly by preventing deposition amyloid fibrils (such as Aβ, tau, α-synuclein), inhibiting microglia activation, reducing release inflammatory factors, restoring mitochondrial membrane prevent oxidative stress, protecting blood-brain barrier, specific enzyme activities cholinesterase). are promising natural agents. By determining pharmacological mechanism, be new candidate

Language: Английский

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Berberine ameliorates iron levels and ferroptosis in the brain of 3 × Tg-AD mice

Phytomedicine, Journal Year: 2023, Volume and Issue: 118, P. 154962 - 154962

Published: July 17, 2023

Language: Английский

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Targeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 4045 - 4055

Published: Feb. 8, 2023

Microtubule-associated protein tau is essential for microtubule assembly and stabilization. Hyperphosphorylation of the microtubule-associated plays an important pathological role in development Alzheimer's disease other tauopathies. In vivo studies using kinase inhibitors suggest that reducing phosphorylation levels has therapeutic potential; however, such approaches showed limited benefits. We sought to further develop our targeting chimera (PhosTAC) technology specifically induce dephosphorylation. Herein, we use small molecule-based PhosTACs recruit PP2A, a native phosphatase. induced formation stable ternary complex, leading rapid, efficient, sustained dephosphorylation, which also correlated with enhanced downregulation protein. Mass spectrometry data validated downregulated multiple sites tau. believe PhosTAC possesses several advantages over current strategies modulate represents new avenue disease-modifying therapies

Language: Английский

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Salivary Biomarkers for Alzheimer’s Disease: A Systematic Review with Meta-Analysis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1168 - 1168

Published: Jan. 18, 2024

Alzheimer’s Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering noninvasive collection of saliva, we designed systematic review answer question “Are salivary biomarkers reliable for diagnosis Disease?” Following inclusion and exclusion criteria, 30 studies were included in this (according PRISMA statement guidelines). Potential include mainly proteins, metabolites even miRNAs. Based on meta-analysis, AD patients, levels beta-amyloid42 p-tau significantly increased, t-tau lactoferrin decreased at borderline statistical significance. However, according pooled AUC, showed a significant predictive value salivary-based diagnosis. In conclusion, potential markers such as beta-amyloid42, tau can be detected saliva could reliably support early disease.

Language: Английский

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Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 279 - 279

Published: Jan. 23, 2025

Alzheimer’s disease (AD) is traditionally viewed through the lens of amyloid cascade hypothesis, implicating amyloid-beta and tau protein aggregates as main pathological culprits. However, burgeoning research points to brain’s resident immune cells, microglia, critical players in AD pathogenesis, progression, potential therapeutic interventions. This review examines dynamic roles microglia within intricate framework AD. We detail involvement these cells neuroinflammation, explaining how their activation response fluctuations may influence trajectory. further elucidate complex relationship between pathology. study highlights dual nature which contribute both aggregation clearance protein. Moreover, an in-depth analysis interplay unveils significant, yet often overlooked, impact this interaction on neurodegeneration Shifting from conventional approaches, we assess current treatments primarily targeting introduce novel strategies that involve manipulating microglial functions. These innovative methods herald a paradigm shift management Finally, explore field precision diagnosis pursuit robust biomarkers. underline more profound comprehension biology could enrich essential areas, potentially paving way for accurate diagnostic tools tailored treatment strategies. In conclusion, expands perspective pathology treatment, drawing attention multifaceted microglia. As continue enhance our understanding microglial-focused interventions emerge promising frontier bolster arsenal fight against

Language: Английский

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Alzheimer’s Disease: The Link Between Amyloid-β and Neurovascular Dysfunction

Journal of Alzheimer s Disease, Journal Year: 2020, Volume and Issue: 76(4), P. 1179 - 1198

Published: June 23, 2020

While prevailing evidence supports that the amyloid cascade hypothesis is a key component of Alzheimer's disease (AD) pathology, many recent studies indicate vascular system also major contributor to progression. Vascular dysfunction and reduced cerebral blood flow (CBF) occur prior accumulation aggregation amyloid-β (Aβ) plaques hyperphosphorylated tau tangles. Although research has predominantly focused on cellular processes involved with Aβ-mediated neurodegeneration, effects Aβ CBF neurovascular coupling are becoming more evident. This review will describe AD disturbances as they relate Aβ, including chronic hypoperfusion, hypertension, altered coupling, deterioration blood-brain barrier. In addition, we findings about relationship between these defects emphasis in vivo utilizing rodent models.

Language: Английский

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