Crosstalk of copper and zinc in the pathogenesis of vascular dementia

Kawahara, Masahiro; Tanaka, Kenichiro; Kato-Negishi, Midori

doi:10.3164/jcbn.22-40

Cited by 6 publications

(8 citation statements)

References 96 publications

(168 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, under pathological conditions such as transient global ischemia, sustained excitation of neurons occurs for prolonged periods in broad areas of the brain, and excess Zn and Cu are simultaneously secreted into the same synaptic clefts for a long period of time. We have demonstrated that a sublethal concentration of Cu (5 µM) significantly exaggerated 30 µM Zn-induced neurotoxicity (molar ratio of Zn:Cu = 6:1) [123]. Therefore, it is possible that the coexistence of Cu triggers the production of ROS and cooperatively enhances Zn-induced neurotoxicity, finally causing vascular-type dementia.…”

Section: Hypothesis: Cross-talk Occurs Between Trace Elements and Amy...mentioning

confidence: 91%

See 1 more Smart Citation

Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases

2023

Self Cite

View full text Add to dashboard Cite

Trace elements such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) are absorbed from food via the gastrointestinal tract, transported into the brain, and play central roles in normal brain functions. An excess of these trace elements often produces reactive oxygen species and damages the brain. Moreover, increasing evidence suggests that the dyshomeostasis of these metals is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, prion diseases, and Lewy body diseases. The disease-related amyloidogenic proteins can regulate metal homeostasis at the synapses, and thus loss of the protective functions of these amyloidogenic proteins causes neurodegeneration. Meanwhile, metal-induced conformational changes of the amyloidogenic proteins contribute to enhancing their neurotoxicity. Moreover, excess Zn and Cu play central roles in the pathogenesis of vascular-type senile dementia. Here, we present an overview of the intake, absorption, and transport of four essential elements (Fe, Zn, Cu, Mn) and one non-essential element (aluminum: Al) in food and their connections with the pathogenesis of neurodegenerative diseases based on metal–protein, and metal–metal cross-talk.

show abstract

Section: Hypothesis: Cross-talk Occurs Between Trace Elements and Amy...mentioning

confidence: 91%

“…Several antioxidants were found to attenuate Cu-enhanced Zn-induced neurotoxicity. Therefore, Cu may collaborate with Zn and play key roles in Zn-induced neurotoxicity by producing ROS, finally leading to the pathogenesis of VD [123].…”

Section: Vascular-type Senile Dementiamentioning

confidence: 99%

Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…This leads to oxidative stress and endoplasmic reticulum stress that may finally lead to neurodegeneration. 44 There is more evidence of zinc and copper related toxicities leading to AD. However, this also may be involved in PD.…”

Section: Insulin-like Growth Factor-1 (Igf-1)mentioning

confidence: 99%

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Soni

Delvadia

Joharapurkar

et al. 2023

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Parkinson's disease (PD) is the second most prevailing progressive disorder leading to neurodegeneration, typically in people above 65 years of age. Motor clinical manifestations of PD appear in a much later stage and include rigidity, tremors, akinesia, and gait dysfunction. There are also nonmotor symptoms like GI and olfactory dysfunction. However, they cannot be considered for diagnosis of the disease, as they are unspecific. PD pathogenesis is mainly characterized by deposits of inclusion bodies on dopaminergic (DA) neurons in substantia nigra pars compacta region (SNpc) of the brain. The major component of these inclusion bodies, are αsynuclein aggregates. α-Synuclein undergoes misfolding and oligomerization to form aggregates and fibrils. These aggregates gradually propagate PD pathology. Other prominent features of this pathological development include mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired autophagy. These all contribute to neuronal degeneration. Besides this, there are many underlying factors which influence these processes. These factors comprise molecular proteins and signaling cascades. In this review, we have listed out underexplored molecular targets that may aid in development of neoteric and advanced therapeutics.

show abstract

“…Moreover, zinc supplementation in high doses compromises copper uptake and vice versa. Adequate zinc and copper homeostasis is known to be important for decades and an altered copper/zinc ratio is found in multiple diseases, such as neurodegenerative disorders [ 125 , 126 ], hepatocellular and gastric carcinoma [ 127 , 128 ], immunological disorders such as sickle cell disease [ 129 ], and bacterial and viral infectious diseases such as leishmaniosis or COVID-19 [ 130 , 131 ]. In future, it may possible that the copper/zinc ratio may be considered as a biomarker for disease or for mortality in the elderly population.…”

Section: Zinc and Nutritional Immunitymentioning

confidence: 99%

Zinc in Human Health and Infectious Diseases

Maywald

Rink

2022

Biomolecules

View full text Add to dashboard Cite

During the last few decades, the micronutrient zinc has proven to be an important metal ion for a well-functioning immune system, and thus also for a suitable immune defense. Nowadays, it is known that the main cause of zinc deficiency is malnutrition. In particular, vulnerable populations, such as the elderly in Western countries and children in developing countries, are often affected. However, sufficient zinc intake and homeostasis is essential for a healthy life, as it is known that zinc deficiency is associated with a multitude of immune disorders such as metabolic and chronic diseases, as well as infectious diseases such as respiratory infections, malaria, HIV, or tuberculosis. Moreover, the modulation of the proinflammatory immune response and oxidative stress is well described. The anti-inflammatory and antioxidant properties of zinc have been known for a long time, but are not comprehensively researched and understood yet. Therefore, this review highlights the current molecular mechanisms underlying the development of a pro-/ and anti-inflammatory immune response as a result of zinc deficiency and zinc supplementation. Additionally, we emphasize the potential of zinc as a preventive and therapeutic agent, alone or in combination with other strategies, that could ameliorate infectious diseases.

show abstract

Crosstalk of copper and zinc in the pathogenesis of vascular dementia

Cited by 6 publications

References 96 publications

Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases

Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Zinc in Human Health and Infectious Diseases

Contact Info

Product

Resources

About