Microglia and Astrocytes in Alzheimer’s Disease in the Context of the Aberrant Copper Homeostasis Hypothesis

Pal, Amit; Rani, Isha; Pawar, Anil; Picozza, Mario; Rongioletti, Mauro; Squitti, Rosanna

doi:10.3390/biom11111598

Cited by 17 publications

(10 citation statements)

References 220 publications

(288 reference statements)

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“…Microglia interact with Aβ and amyloid-beta precursor protein (APP) through specific pattern-recognition receptors, including CD14, CD36, and Toll-like receptors, which are strongly expressed on the microglial surface [ 44 ]. This interaction increases microglial phagocytosis, resulting in the clearance of Aβ from the brain [ 45 , 46 ]. As an example, the phagocytic index and total Aβ load are higher in IL-1α (+) and IL-1Ra (+) microglia and microglia producing TNF-α and IL-1β are associated with a lower Aβ load and phagocytic index in AD mice [ 47 ].…”

Section: Microglia Are a “Double-edged Sword” In The Progression Of Admentioning

confidence: 99%

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders

et al. 2023

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As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.

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Section: Microglia Are a “Double-edged Sword” In The Progression Of Admentioning

confidence: 99%

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders

et al. 2023

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“…Copper (DB09130) is a transition metal and a trace element in the body. Copper imbalance is associated with the pathogenesis of AD, which is an avenue for new therapeutic strategies (Ejaz et al, 2020 ; Zhu et al, 2020 ; Zubčić et al, 2020 ; Lei et al, 2021 ; Pal et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Lai

Liu

et al. 2022

Front. Aging Neurosci.

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Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.

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“…[88] This interaction promotes phagocytosis, leading to the clearance of A𝛽 from the brain. [89,90] Microglia producing TNF-𝛼 and IL-1𝛽 have shown higher phagocytic activity in AD mice. [91] Strategies aimed at modulating microglial activation by inhibiting the release of inflammatory factors are highly desired, and in this regard, preclinical studies have demonstrated that blocking TNF or IL-1 receptors through genetic or pharmacological approaches can reduce amyloid pathology and tau phosphorylation.…”

Section: Microglia Role In Alzheimer's Diseasementioning

confidence: 99%

Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders

Battaglini,

Marino,

Montorsi

et al. 2024

Adv Healthcare Materials

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Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro‐inflammatory classical phenotype, M1, and anti‐inflammatory alternative phenotype, M2. Despite their pivotal role in CNS homeostasis, microglia phenotypes can influence the development and progression of several CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injuries, and even brain cancer. It is thus clear as the possibility of modulating microglia activation has gained attention as a therapeutic tool against many CNS pathologies. Nanomaterials are an unprecedented tool for manipulating microglia responses, in particular to specifically target microglia and elicit an in situ immunomodulation activity. In this review we will focus our discussion on two main aspects: we will analyze the possibility of using nanomaterials to stimulate a pro‐inflammatory response of microglia against brain cancer and we will introduce nanostructures able to foster an anti‐inflammatory response for treating neurodegenerative disorders. The final aim is to stimulate the analysis of the development of new microglia nano‐immunomodulators, paving the way for innovative and effective therapeutic approaches for the treatment of CNS disorders.This article is protected by copyright. All rights reserved

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Microglia and Astrocytes in Alzheimer’s Disease in the Context of the Aberrant Copper Homeostasis Hypothesis

Cited by 17 publications

References 220 publications

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders

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