Copper enhances aggregational toxicity of mutant huntingtin in a Drosophila model of Huntington's Disease

Lobato, Amanda G.; Ortiz-Vega, Natalie; Zhu, Yi; Neupane, Deepa; Meier, Katlyn K.; Zhai, R. Grace

doi:10.1016/j.bbadis.2023.166928

Cited by 4 publications

(2 citation statements)

References 60 publications

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“…Cu, as mentioned earlier, is an essential metal that plays a critical role in various neurochemical processes, where its dysregulation is detrimental [132]. Studies highlight its potential contribution to neurodegeneration in HD via enhancement of the mHTT toxicity [14]. Cu may also disrupt proteostasis, the process of protein folding and degradation, further contributing to cellular dysfunction [133].…”

Section: Copper (Cu) -Hdmentioning

confidence: 99%

“…Thus, like Fe, Cu may promote mHTT aggregation and toxicity. Cu also modulates the interaction between huntingtin inclusions and the autophagy adaptor protein, which is responsible for clearance of the toxic aggregate [14,[135][136][137]. A study using the drosophila model of HD showed that D-penicillamine, a Cu chelator, significantly reduced the formation of amyloid-like huntingtin aggregates, suggesting a potential therapeutic avenue for mitigating the toxicity associated with huntingtin aggregation [14].…”

Section: Copper (Cu) -Hdmentioning

confidence: 99%

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Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Tizabi,

Bennani,

El Kouhen

et al. 2024

Preprint

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Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since HTT protein is involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations, however, at higher concentrations, can exacerbate HD by disrupting the glial-neuronal communication, and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for development of a new generation of disease-modifying therapies in HD.

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Section: Copper (Cu) -Hdmentioning

confidence: 99%

Section: Copper (Cu) -Hdmentioning

confidence: 99%

Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Tizabi,

Bennani,

El Kouhen

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Copper homeostasis and cuproptosis in health and disease

Yang,

Wu,

Wang

et al. 2024

MedComm

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Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation of various biological processes. Regulation of copper levels within a narrow range is imperative for maintaining metabolic homeostasis. Numerous studies have demonstrated the significant roles of copper homeostasis and cuproptosis in health and disease pathogenesis. However, a comprehensive and up‐to‐date systematic review in this domain remains absent. This review aims to consolidate recent advancements in understanding the roles of cuproptosis and copper homeostasis in health and disease, focusing on the underlying mechanisms and potential therapeutic interventions. Dysregulation of copper homeostasis, manifesting as either copper excess or deficiency, is implicated in the etiology of various diseases. Cuproptosis, a recently identified form of cell death, is characterized by intracellular copper overload. This phenomenon mediates a diverse array of evolutionary processes in organisms, spanning from health to disease, and is implicated in genetic disorders, liver diseases, neurodegenerative disorders, and various cancers. This review provides a comprehensive summary of the pathogenic mechanisms underlying cuproptosis and copper homeostasis, along with associated targeted therapeutic agents. Furthermore, it explores future research directions with the potential to yield significant advancements in disease treatment, health management, and disease prevention.

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Copper: From enigma to therapeutic target for neurological disorder

Patwa,

Flora

2024

Basic Clin Pharma Tox

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Neurological disorders (NDs) have a negative impact on the lives of individuals. There could be two explanations for this: unclear aetiology and lack of effective therapy. However, research in the past few years has revealed the role of bio‐metals dyshomeostasis in NDs. The imbalance in copper (Cu) concentration may be one of the main causative factors in NDs. In this review, we have discussed the role of Cu in NDs, especially Alzheimer's disease (AD), including the molecular mechanisms involved in Cu‐associated NDs like oxidative stress, neuroinflammation, and protein misfolding. We have also summarized the recent Cu‐targeting approaches and highlighted the in vitro and in vivo studies recently being reported on the subject. Based on the earlier published reports, it could be speculated that the Cu targeting strategy might be an interesting and potential therapeutic approach for NDs. Various difficulties must be overcome to develop safe and efficient Cu‐targeting medications for NDs.

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Copper enhances aggregational toxicity of mutant huntingtin in a Drosophila model of Huntington's Disease

Cited by 4 publications

References 60 publications

Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Copper homeostasis and cuproptosis in health and disease

Copper: From enigma to therapeutic target for neurological disorder

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