The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

Liu, Hilary Y.; Gale, Jenna R.; Reynolds, Ian J.; Weiss, John H.; Aizenman, Elias

doi:10.3390/biomedicines9050489

Cited by 24 publications

(14 citation statements)

References 271 publications

(441 reference statements)

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“…Zinc is an essential trace metal that plays a significant role in several processes, such as cell growth and differentiation, stabilisation of nucleic acid and protein structure, cellular signalling and neurotransmission [ 42 , 43 , 84 , 102 ]. Conversely, Zn dyshomeostasis may contribute to pathomechanisms of numerous brain diseases [ 103 ].…”

Section: Glucose and Pyruvate-derived Acetyl-coa Metabolism In Cholin...mentioning

confidence: 99%

Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

Jankowska-Kulawy

Klimaszewska-Łata

Gul-Hinc

et al. 2022

IJMS

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The human brain is characterised by the most diverse morphological, metabolic and functional structure among all body tissues. This is due to the existence of diverse neurons secreting various neurotransmitters and mutually modulating their own activity through thousands of pre- and postsynaptic interconnections in each neuron. Astroglial, microglial and oligodendroglial cells and neurons reciprocally regulate the metabolism of key energy substrates, thereby exerting several neuroprotective, neurotoxic and regulatory effects on neuronal viability and neurotransmitter functions. Maintenance of the pool of mitochondrial acetyl-CoA derived from glycolytic glucose metabolism is a key factor for neuronal survival. Thus, acetyl-CoA is regarded as a direct energy precursor through the TCA cycle and respiratory chain, thereby affecting brain cell viability. It is also used for hundreds of acetylation reactions, including N-acetyl aspartate synthesis in neuronal mitochondria, acetylcholine synthesis in cholinergic neurons, as well as divergent acetylations of several proteins, peptides, histones and low-molecular-weight species in all cellular compartments. Therefore, acetyl-CoA should be considered as the central point of metabolism maintaining equilibrium between anabolic and catabolic pathways in the brain. This review presents data supporting this thesis.

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Section: Glucose and Pyruvate-derived Acetyl-coa Metabolism In Cholin...mentioning

confidence: 99%

Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

Jankowska-Kulawy

Klimaszewska-Łata

Gul-Hinc

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Experiment carried out on mouse cortical cultures showed mitochondrial ROS production induced by zinc, possibly via inhibition of the lipoamide dehydrogenase (LADH) component of alpha-ketoglutarate dehydrogenase complex (KGDHC) in the TCA cycle [ 42 , 43 ]. LADH catalyses NAD + reduction to NADH, but zinc inhibits this process and favours NADH oxidation in the mitochondrial matrix.…”

Section: Sources Of Ros Generation In Neuronsmentioning

confidence: 99%

Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders

Akanji

Rotimi

Elebiyo

et al. 2021

Oxidative Medicine and Cellular Longevity

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Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

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“…In addition, zinc accumulation has been shown to cause mitochondrial dysfunction and oxidative stress in AD (Sensi et al, 2003;Liu et al, 2021) as well as in ischemic stroke models (Ji et al, 2018;Zhao et al, 2018). Mitochondrial Zn 2+ accumulation is a possible trigger of hippocampal ischemic injury (Ji et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway

Chen

Lai

et al. 2022

Front. Pharmacol.

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Zinc is an essential trace element important for the physiological function of the central nervous system. The abnormal accumulation of zinc inside neurons may induce mitochondrial dysfunction and oxidative stress, which contribute to many brain diseases. We hypothesized that natural anthraquinone derivative emodin can protect against neurotoxicity induced by pathological concentrations of zinc via the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and alleviate oxidative stress and mitochondrial dysfunction. Human neuroblastoma (SH-SY5Y 26 cells) was treated with zinc sulfate and different concentrations of emodin, and changes in the levels of ETK1/2 expression, oxidative stress (DCFH-DA staining), mitochondrial function (JC-1 staining), lipid peroxidation (4-hydroxynonenal staining), and DNA oxidation (8-hydroxy-2-deoxyguanosine staining) were examined. Emodin ameliorated zinc-induced altered expression of levels of phosphorylated ERK1/2 (not total ETK1/2) and synaptic proteins (presynaptic SNAP 25, synaptophysin and postsynaptic PSD95) in SH-SY5Y cells. Moreover, emodin inhibited the generation of reactive oxygen species and oxidative stress and facilitated the collapse of mitochondrial membrane potential (ΔΨm) in SH-SY5Y cells. In conclusion, our results indicated that emodin exerts neuroprotective effects against zinc by normalizing synaptic impairment by decreasing the phosphorylation of ERK1/2, reducing reactive oxygen species and protecting mitochondrial function.

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The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

Cited by 24 publications

References 271 publications

Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders

Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway

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