Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer’s disease

Lim, Siok Lam; Rodriguez‐Ortiz, Carlos J.; Hsu, Heng-Wei; Wu, Jie; Zumkehr, Joannee; Kilian, Jason; Vidal, Janielle; Ayata, Pinar; Kitazawa, Masashi

doi:10.1016/j.jtemb.2020.126578

Cited by 16 publications

(10 citation statements)

References 60 publications

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“…Moreover, it has been demonstrated that copper ions in culture medium induce the transformation of the macrophage phenotype to the proinflammatory M1 state by activating copper transport signaling [115]. Furthermore, a recent report shows that copper changes the microglia phenotype to a degenerative phenotype [116].…”

Section: Interplay Of Copper Aβ and Microglia Activation In Mediating Nmda Receptor-induced Excitotoxicitymentioning

confidence: 99%

Probable Reasons for Neuron Copper Deficiency in the Brain of Patients with Alzheimer’s Disease: The Complex Role of Amyloid

et al. 2022

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Alzheimer’s disease is a progressive neurodegenerative disorder that eventually leads the affected patients to die. The appearance of senile plaques in the brains of Alzheimer’s patients is known as a main symptom of this disease. The plaques consist of different components, and according to numerous reports, their main components include beta-amyloid peptide and transition metals such as copper. In this disease, metal dyshomeostasis leads the number of copper ions to simultaneously increase in the plaques and decrease in neurons. Copper ions are essential for proper brain functioning, and one of the possible mechanisms of neuronal death in Alzheimer’s disease is the copper depletion of neurons. However, the reason for the copper depletion is as yet unknown. Based on the available evidence, we suggest two possible reasons: the first is copper released from neurons (along with beta-amyloid peptides), which is deposited outside the neurons, and the second is the uptake of copper ions by activated microglia.

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Section: Interplay Of Copper Aβ and Microglia Activation In Mediating Nmda Receptor-induced Excitotoxicitymentioning

confidence: 99%

Probable Reasons for Neuron Copper Deficiency in the Brain of Patients with Alzheimer’s Disease: The Complex Role of Amyloid

et al. 2022

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“…Detection of copper is useful in the diagnosis and prevention of AD[ 22 , 23 ]. In addition, long-term exposure to copper is associated with cognitive decline and microglia degeneration[ 24 ]. TDMQ20 was shown to reduce the copper content in the cerebral cortex of mice[ 25 ], and ameliorate oxidative stress in the cerebral cortex of mice, further attenuating the neurotoxicity of amyloid[ 26 ].…”

Section: Ad and Micronutrientsmentioning

confidence: 99%

Role of micronutrients in Alzheimer's disease: Review of available evidence

Hong-xin¹,

Qian²,

Wu³

et al. 2022

WJCC

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Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders that have been studied for more than 100 years. Although an increased level of amyloid precursor protein is considered a key contributor to the development of AD, the exact pathogenic mechanism remains known. Multiple factors are related to AD, such as genetic factors, aging, lifestyle, and nutrients. Both epidemiological and clinical evidence has shown that the levels of micronutrients, such as copper, zinc, and iron, are closely related to the development of AD. In this review, we summarize the roles of eight micronutrients, including copper, zinc, iron, selenium, silicon, manganese, arsenic, and vitamin D in AD based on recently published studies.

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“…A recent in vivo transcriptomic analysis of microglia in neurodegeneration has highlighted that excess Cu intake through drinking water shifts the microglial phenotype towards degenerative expression by increasing the translation of degenerative genes and repressing homeostatic genes, which thereby accelerates cognitive decline and may illustrate one of the major mechanisms linking Cu dyshomeostasis to the AD pathology [ 169 ]. In vivo and in vitro analysis have suggested that Cu(II) diminishes the microglia-mediated clearance of Aβ 1–42 via modulating the mammalian target of rapamycin (mTOR) transcription factor EB (TFEB) axis attributable for the suppression or impairment of lysosomal biogenesis and autophagic flux.…”

Section: Altered Cu Homeostasis In Microglia and Astrocyte In Admentioning

confidence: 99%

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

et al. 2021

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Evidence of copper’s (Cu) involvement in Alzheimer’s disease (AD) is available, but information on Cu involvement in microglia and astrocytes during the course of AD has yet to be structurally discussed. This review deals with this matter in an attempt to provide an updated discussion on the role of reactive glia challenged by excess labile Cu in a wide picture that embraces all the major processes identified as playing a role in toxicity induced by an imbalance of Cu in AD.

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Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer’s disease

Cited by 16 publications

References 60 publications

Probable Reasons for Neuron Copper Deficiency in the Brain of Patients with Alzheimer’s Disease: The Complex Role of Amyloid

Probable Reasons for Neuron Copper Deficiency in the Brain of Patients with Alzheimer’s Disease: The Complex Role of Amyloid

Role of micronutrients in Alzheimer's disease: Review of available evidence

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

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