Molecular mechanisms of ischemia and glutamate excitotoxicity

Neves, Diogo; Salazar, Ivan L.; Almeida, Ramiro D.; Silva, Raquel M.

doi:10.1016/j.lfs.2023.121814

Cited by 57 publications

(15 citation statements)

References 188 publications

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“…This process contributes to the production of glutathione, enabling the mitigation of reactive oxygen species (ROS) and the alleviation of oxidative stress in cancer cells [ 36 ]. The accumulation of glutamate in the extracellular milieu can lead to the overstimulation of its membrane receptors, such as NMDAR, leading to cell injury or death, a condition known as excitotoxicity in neurons [ 37 ]. We show that NMDAR2B, the subunit that binds glutamate, is cleaved at the N-terminus in Hek293T cells and BT-549 TNBC cells.…”

Section: Discussionmentioning

confidence: 99%

MET Oncogene Enhances Pro-Migratory Functions by Counteracting NMDAR2B Cleavage

Gallo,

Vitacolonna,

Comoglio

et al. 2023

Cells

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The involvement of the N-methyl-D-aspartate receptor (NMDAR), a glutamate-gated ion channel, in promoting the invasive growth of cancer cells is an area of ongoing investigation. Our previous findings revealed a physical interaction between NMDAR and MET, the hepatocyte growth factor (HGF) receptor. However, the molecular mechanisms underlying this NMDAR/MET interaction remain unclear. In this study, we demonstrate that the NMDAR2B subunit undergoes proteolytic processing, resulting in a low-molecular-weight form of 100 kDa. Interestingly, when the NMDAR2B and MET constructs were co-transfected, the full-size high-molecular-weight NMDAR2B form of 160 kDa was predominantly observed. The protection of NMDAR2B from cleavage was dependent on the kinase activity of MET. We provide the following evidence that MET opposes the autophagic lysosomal proteolysis of NMDAR2B: (i) MET decreased the protein levels of lysosomal cathepsins; (ii) treatment with either an inhibitor of autophagosome formation or the fusion of the autophagosome and lysosome elevated the proportion of the NMDAR2B protein’s uncleaved form; (iii) a specific mTOR inhibitor hindered the anti-autophagic effect of MET. Finally, we demonstrate that MET coopts NMDAR2B to augment cell migration. This implies that MET harnesses the functionality of NMDAR2B to enhance the ability of cancer cells to migrate.

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Section: Discussionmentioning

confidence: 99%

MET Oncogene Enhances Pro-Migratory Functions by Counteracting NMDAR2B Cleavage

Gallo,

Vitacolonna,

Comoglio

et al. 2023

Cells

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“…However, uncontrolled NMDAR activity promotes excitotoxicity and cell mortality, which has been reported in AD. Glutamate-induced excitotoxicity is a key mechanism that leads to chronic neurodegeneration and acute neuronal injuries [ 74 ]. In this case, 1MeTIQ is a crucial component in providing neuroprotection by inhibiting the glutamate-induced excitotoxicity mechanism.…”

Section: Tetrahydroisoquinoline Derivativesmentioning

confidence: 99%

A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

Thangeswaran,

Shamsuddin,

Balakrishnan

2024

Heliyon

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“…The intracellular homeostasis is disrupted after SCI, characterized by increased excitotoxicity of glutamate, elevated levels of free iron, and increased membrane permeability of Ca 2+ ( 21 ). The elevated intracellular Ca 2+ levels activate the nicotinamide adenine dinucleotide, which promotes ATP production while also increasing the production of ROS ( 22 , 23 ). Excessive ROS can increase the permeability of Ca 2+ membranes, leading to an increased influx of Ca 2+ , which causes a decrease in membrane potential.…”

Section: The Relationship Between Sci With Oxidative Stressmentioning

confidence: 99%

Research progress on the inhibition of oxidative stress by teriparatide in spinal cord injury

Ai,

Xiong,

Deng

et al. 2024

Front. Neurol.

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Spinal cord injury (SCI) is currently a highly disabling disease, which poses serious harm to patients and their families. Due to the fact that primary SCI is caused by direct external force, current research on SCI mainly focuses on the treatment and prevention of secondary SCI. Oxidative stress is one of the important pathogenic mechanisms of SCI, and intervention of oxidative stress may be a potential treatment option for SCI. Teriparatide is a drug that regulates bone metabolism, and recent studies have found that it has the ability to counteract oxidative stress and is closely related to SCI. This article summarizes the main pathological mechanisms of oxidative stress in SCI, as well as the relationship between them with teriparatide, and explores the therapeutic potential of teriparatide in SCI.

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Molecular mechanisms of ischemia and glutamate excitotoxicity

Cited by 57 publications

References 188 publications

MET Oncogene Enhances Pro-Migratory Functions by Counteracting NMDAR2B Cleavage

MET Oncogene Enhances Pro-Migratory Functions by Counteracting NMDAR2B Cleavage

A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

Research progress on the inhibition of oxidative stress by teriparatide in spinal cord injury

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