A1/A2 astrocytes in central nervous system injuries and diseases: Angels or devils?

Neurochemistry International, Год журнала: 2021, Номер 148, С. 105080 - 105080

Опубликована: Май 25, 2021

Язык: Английский

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Alzheimer’s disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs

Biochemical Pharmacology, Год журнала: 2023, Номер 211, С. 115522 - 115522

Опубликована: Март 28, 2023

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions people worldwide, with both prevalence and incidence increasing age. It characterized by cognitive decline associated, specifically, degeneration cholinergic neurons. The problem this even more fundamental as available therapies remain fairly limited mainly focused on symptoms' relief. Although aetiology remains elusive, two main pathological hallmarks are described: i) presence neurofibrillary tangles formed unfolded protein aggregates (hyperphosphorylated Tau protein) ii) extracellular amyloid-beta peptide. Given complexity surrounding pathogenesis disease, several potential targets have been highlighted interrelated upon its progression, such oxidative stress accumulation metal ions. Thus, advances made development innovative multitarget therapeutical compounds to delay progression restore cell function. This review focuses ongoing research new insights emerging disease-modifying drugs for AD treatment. Furthermore, classical novel biomarkers early diagnosis their role in assisting improvement targeted will also be approached.

Язык: Английский

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Glial cells in Alzheimer’s disease: From neuropathological changes to therapeutic implications

Ageing Research Reviews, Год журнала: 2022, Номер 78, С. 101622 - 101622

Опубликована: Апрель 12, 2022

Язык: Английский

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Advancing cell therapy for neurodegenerative diseases

Cell stem cell, Год журнала: 2023, Номер 30(5), С. 512 - 529

Опубликована: Апрель 20, 2023

Язык: Английский

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The Vitamin D Receptor as a Potential Target for the Treatment of Age-Related Neurodegenerative Diseases Such as Alzheimer’s and Parkinson’s Diseases: A Narrative Review

Cells, Год журнала: 2023, Номер 12(4), С. 660 - 660

Опубликована: Фев. 19, 2023

The vitamin D receptor (VDR) belongs to the nuclear superfamily of transcription factors. VDR is expressed in diverse brain regions and has been implicated neuroprotective, antiaging, prosurvival, anti-inflammatory action D. Accordingly, a relationship between insufficiency susceptibility neurodegenerative diseases suggested. However, due multitargeted mechanisms its often overlapping genomic nongenomic effects, role pathologies remains obscure. In this narrative review, we present progress deciphering molecular mechanism VDR-mediated effects on prosurvival signaling pathway activity within central nervous system. line with concept neurovascular unit pathomechanisms diseases, discussion regulating immune vascular systems also included. Next, discuss results preclinical clinical studies evaluating significance status efficacy supplementation treatment Parkinson’s Alzheimer’s emphasizing possible these phenomena. Finally, associations some polymorphisms higher risks severity disorders are briefly summarized.

Язык: Английский

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First-in-Humans Evaluation of ¹⁸F-SMBT-1, a Novel ¹⁸F-Labeled Monoamine Oxidase-B PET Tracer for Imaging Reactive Astrogliosis

Journal of Nuclear Medicine, Год журнала: 2022, Номер 63(10), С. 1551 - 1559

Опубликована: Янв. 27, 2022

Background: Reactive gliosis changes, characterized by reactive astrocytes and activated microglia, contribute greatly to neurodegeneration throughout the course of Alzheimer's disease (AD). overexpress monoamine oxidase-B (MAO-B). We clinical performance ¹⁸F-SMBT-1, a novel MAO-B PET tracer as potential surrogate marker astrogliosis. Methods: Seventy-seven participants –53 controls (CN), 7 mild cognitively impaired (MCI), AD patients, 10 young (YCN)– were recruited for different aspects study. Older underwent 3D-MPRAGE MRI Aβ, tau, ¹⁸F-SMBT-1 imaging with PET. To ascertain selectivity MAO-B, 9 two scans, before after receiving 5mg selegiline twice daily 5 days. compare selectivity, ¹⁸F-THK5351 studies also conducted selegiline. Aβ burden was expressed in Centiloids. outcomes standard uptake value, well tissue ratios binding parameters using subcortical white matter reference region. Results:¹⁸F-SMBT-1 showed robust entry into brain reversible kinetics, high retention basal ganglia, intermediate cortical regions, lowest cerebellum which tightly follows known regional distribution (R2=0.84). More than 85% signal blocked across and, contrast ¹⁸F-THK5351, no residual activity observed regimen, indicating low non-specific binding. captured increases age, an annual rate change (~2.6%/yr), similar vitro rates (~1.9%/yr). Quantitative semiquantitative measures highly associated (R2>0.94), suggesting simplified ratio approach could be used generate outcome measures. Conclusion:¹⁸F-SMBT-1 is selective tracer, binding, displaying kinetics. Moreover, matches reported captures can potentially Further validation these findings will require examination much larger series, including MCI AD.

Язык: Английский

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Foundations and implications of astrocyte heterogeneity during brain development and disease

Trends in Neurosciences, Год журнала: 2022, Номер 45(9), С. 692 - 703

Опубликована: Июль 23, 2022

Язык: Английский

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Assessing Reactive Astrogliosis with ¹⁸F-SMBT-1 Across the Alzheimer Disease Spectrum

Journal of Nuclear Medicine, Год журнала: 2022, Номер 63(10), С. 1560 - 1569

Опубликована: Янв. 27, 2022

Background: Neuroinflammatory reaction in Alzheimer's disease (AD) brains involves reactive astrocytes which overexpress monoamine oxidase-B (MAO-B). ¹⁸F-SMBT-1 is a novel F-18 PET tracer highly selective for MAO-B. We characterized the clinical performance of across continuum as potential surrogate marker astrogliosis Methods: assessed regional binding 77 volunteers (76±5.5 y.o.; 41F/36M) AD continuum: 57 cognitively unimpaired controls (CN, 44 Aβ- & 13 Aβ+), 12 mild impaired (MCI, 9 3 and 8 dementia patients (6 Aβ+ 2 Aβ-). All participants also underwent Aβ tau imaging, 3T MRI neuropsychological evaluation. Tau imaging results were expressed standard uptake value ratios (SUVR) using cerebellar cortex reference region, while burden was Centiloids. outcomes SUVR subcortical white matter region. Results:¹⁸F-SMBT-1 yielded high contrast images at steady state (60-80 min after injection). When compared to Aβ-CN, there no significant differences Aβ-MCI group. Conversely, significantly higher several cortical regions Aβ+AD group, but lower mesial temporal basal ganglia. Most importantly, same Aβ+CN when Aβ-CN. all groups considered together, correlated with burden, much less burden. While most not brain volumetrics, known MAO-B concentrations presented direct association hippocampal grey volumes, occipital lobe directly associated hyperintensities. inversely MMSE AIBL PACC some neocortical such frontal cortex, lateral supramarginal gyrus. Conclusion: Cross-sectional human studies ¹⁸F-SMBT-1, showed that Aβ+AD, have than CN. Moreover, brain, retention load. These findings suggest increased detectable preclinical stages accumulation, providing strong support its use continuum.

Язык: Английский

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An insight into the neuroprotective and anti-neuroinflammatory effects and mechanisms of Moringa oleifera

Frontiers in Pharmacology, Год журнала: 2023, Номер 13

Опубликована: Янв. 5, 2023

Neurodegenerative diseases (NDs) are sporadic maladies that affect patients’ lives with progressive neurological disabilities and reduced quality of life. Neuroinflammation oxidative reaction among the pivotal factors for neurodegenerative conditions, contributing to progression NDs, such as Parkinson’s disease (PD), Alzheimer’s (AD), multiple sclerosis (MS) Huntington’s (HD). Management NDs is still less than optimum due its wide range causative influences, lifestyle, genetic variants, environmental aspects. The neuroprotective anti-neuroinflammatory activities Moringa oleifera have been documented in numerous studies richness phytochemicals antioxidant anti-inflammatory properties. This review highlights up-to-date research findings on effects M. , including mechanisms against NDs. information was gathered from databases, which include Scopus, Science Direct, Ovid-MEDLINE, Springer, Elsevier. Neuroprotective were mainly assessed by using crude extracts vitro vivo experiments. Isolated compounds moringin, astragalin, isoquercitrin, identified phenolic acids flavonoids (chlorogenic acid, gallic ferulic caffeic kaempferol, quercetin, myricetin, (-)-epicatechin, isoquercitrin) reported neuropharmacological activities. Therefore, these may potentially contribute effects. More in-depth animal models neurological-related disorders extensive preclinical investigations, pharmacokinetics, toxicity, bioavailability necessary before clinical trials can be carried out develop constituents into agents.

Язык: Английский

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Activators of Nrf2 to Counteract Neurodegenerative Diseases

Antioxidants, Год журнала: 2023, Номер 12(3), С. 778 - 778

Опубликована: Март 22, 2023

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration loss of nerve cells. Oxidative stress has been proposed as one factor plays a potential role the pathogenesis neurodegenerative disorders since neuron cells particularly vulnerable to oxidative damage. Nuclear (erythroid-derived 2)-like 2 (Nrf2) is strictly related anti-inflammatory antioxidative cell response; therefore, its activation consequent enhancement cellular pathways have therapeutic approach. Several Nrf2 activators with different mechanisms diverse structures reported, but those applied for neurodisorders still limited. However, very last few years, interesting progress made, enhancing blood–brain barrier penetration, make effective drugs, designing Nrf2-based multitarget-directed ligands affect multiple involved pathology diseases. The present review gives an overview most representative findings this research area.

Язык: Английский

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