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Cited by 38Trace Elements in HealthHeavy Metal Exposure and ToxicityNeurological diseases and metabolism

Copper neurotoxicity: Induction of cognitive dysfunction: A review

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Feng, Duan, Zhao, Yu, Li, Wei, Li, Xuechao, Wan, Jixiang, Wang, Fangjun·2023·Medicine
DOI 10.1097/md.0000000000036375PMC PMC10695595
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Abstract

Cognitive dysfunction occurs mainly in certain diseases and in the pathological process of aging. In addition to this, it is also widespread in patients undergoing anesthesia, surgery, and cancer chemotherapy. Neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired synaptic plasticity, and lack of neurotrophic support are involved in copper-induced cognitive dysfunction. In addition, recent studies have found that copper mediates cuproptosis and adversely affects cognitive function. Cuproptosis is a copper-dependent, lipoylated mitochondrial protein-driven, non-apoptotic mode of regulated cell death, which provides us with new avenues for identifying and treating related diseases. However, the exact mechanism by which cuproptosis induces cognitive decline is still unclear, and this has attracted the interest of many researchers. In this paper, we analyzed the pathological mechanisms and therapeutic targets of copper-associated cognitive decline, mainly in the context of neurodegenerative diseases, psychiatric and psychological disorders, and diabetes mellitus.

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  • Copper is implicated in cuproptosis, a form of cell death mediated by direct binding of Cu+ to lipoylated DLAT, leading to its aggregation and proteotoxic stress.

    “Recent studies also implicate copper in cuproptosis, a novel form of cell death mediated by direct binding of Cu⁺ to lipoylated dihydrolipoyl transacetylase (DLAT), leading to its aggregation and proteotoxic stress [111].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [111]

    Section 3.2 (page not provided) says copper directly binds DLAT, promotes aggregation of lipoylated DLAT, and leads to proteotoxic stress and cuproptosis. It does not identify the directly binding copper as Cu⁺; the Introduction instead describes cuproptosis as triggered by excess Cu²⁺. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Feng, D., Zhao, Y., Li, W., Li, X., Wan, J., & Wang, F.
Affiliations
  • Affiliated Hospital of North Sichuan Medical College (CN)
  • General Surgery Department, Enyang District People’s Hospital, Bazhong City, China
  • ICU, Bazhong District People’s Hospital, Bazhong, China.
Corresponding author
Wang, Fangjun
ORCID
Venue
Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2023-12-01
Volume
102
Issue
48
Pages
e36375
ISSN
  • 0025-7974 (ISSN-L)
  • 1536-5964
DOI
10.1097/md.0000000000036375
PMC
PMC10695595
OpenAlex
W4389257744
Cited by
38
References
3
Citations by year
2026: 14 · 2025: 14 · 2024: 10
FWCI
1.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
copper neurotoxicity, cognitive impairment, cuproptosis, neuroinflammation, oxidative stress, mitochondrial dysfunction, synaptic plasticity, neurotrophic support, neurodegenerative diseases, mental illness, diabetes mellitus, aging, chemotherapy
MeSH terms
Aging, Copper, Humans, Apoptosis, Oxidative Stress, Neurodegenerative Diseases, Cognitive Dysfunction

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