Increased LCN2/iron complex binds to SLC22A17 receptor in neuron

GO:0036475

GO neuron death in response to oxidative stress

WIKI increased

9606

NCBI Homo sapiens

Increased LCN2/iron complex binds to SLC22A17 receptor in neuron

Increased LCN2/iron complex

Molecular

AOPWiki 2023-06-15T04:36:21

2023-06-15T04:36:21

Increased intracelluar Iron accumulation

Increased intracelluar Iron

Cellular

AOPWiki 2023-06-15T04:38:20

2023-06-15T04:38:20

Neuronal dysfunction

Cellular

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible? It is possible to use several markers of neuronal cytoskeleton (e.g. : neurofimanent proteins, NF-L, -M, -H), synapses (e.g.: synaptophysin), neurotransmitters or enzymes involved in neurotransmitter synthesis (e.g.: thyrosine hydroxylase) and look for changes at the mRNA level with quantitative RT-PCR and at the protein level, with immunoblotting (ex. thyrosine hydroxylase, NF-L,-M,-H), immunocytochemistry followed by a quantification, or by enzymatic assays (e.g.: choline acetyltransferase, glutamic acid decarboxylase). Genomic, proteomic and metabolomic approaches are also suitable for a non targeted approach. All these techniques are widely used, but for a recent description in the context of neurotoxicology and neuroinflammation, see Sandström et al., 2014, von Tobel et al., 2014, Monnet-Tschudi et al., 2000).

CL:0000540

CL neuron

Choi WS, Abel G, Klintworth H, Flavell RA, Xia Z (2010) JNK3 mediates paraquat- and rotenone-induced dopaminergic neuron death. J Neuropathol Exp Neurol 69: 511-520 Corvino V, Marchese E, Michetti F, Geloso MC (2013) Neuroprotective strategies in hippocampal neurodegeneration induced by the neurotoxicant trimethyltin. Neurochem Res 38: 240-253 Janigro D, Costa LG (1987) Effects of trimethyltin on granule cells excitability in the in vitro rat dentate gyrus. Neurotoxicol Teratol 9: 33-38 Klintworth H, Garden G, Xia Z (2009) Rotenone and paraquat do not directly activate microglia or induce inflammatory cytokine release. Neurosci Lett 462: 1-5 Monnet-Tschudi F, Zurich MG, Honegger P (1996) Comparison of the developmental effects of two mercury compounds on glial cells and neurons in aggregate cultures of rat telencephalon. Brain Res 741: 52-59 Monnet-Tschudi F, Zurich MG, Schilter B, Costa LG, Honegger P (2000) Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures. Toxicol Appl Pharmacol 165: 175-183 Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308: 1314-1318 Sandström von Tobel, J., D. Zoia, et al. (2014a). "Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures." Toxicol Lett. DOI : 10.1016/j.toxlet.2014.02.001 Sanfeliu C, Sebastia J, Cristofol R, Rodriguez-Farre E (2003) Neurotoxicity of organomercurial compounds. Neurotox Res 5: 283-305 Stansfield KH, Pilsner JR, Lu Q, Wright RO, Guilarte TR (2012) Dysregulation of BDNF-TrkB signaling in developing hippocampal neurons by Pb(2+): implications for an environmental basis of neurodevelopmental disorders. Toxicol Sci 127: 277-295 von Tobel, J. S., P. Antinori, et al. (2014b). "Repeated exposure to Ochratoxin A generates a neuroinflammatory response, characterized by neurodegenerative M1 microglial phenotype." Neurotoxicology 44C: 61-70. Xanthos DN, Sandkühler J (2014). Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity. Nat Rev Neurosci. 2014 Jan;15(1):43-53. AOPWiki 2016-11-29T18:41:23

2022-04-07T09:32:56

Neurological disorder

Individual

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2023-06-15T04:43:04

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b431396fdf8> AOPWiki 2023-06-15T04:44:32

2023-06-15T04:44:32

<upstream-id>628bc0fd-a49b-4b98-8a06-6a6bfda28e35</upstream-id> <downstream-id>84301d26-e89f-4b05-a37e-ea2e13de49b7</downstream-id>

#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b43139c22b0> AOPWiki 2023-06-15T04:45:00

2023-06-15T04:45:00

<upstream-id>84301d26-e89f-4b05-a37e-ea2e13de49b7</upstream-id> <downstream-id>6c0170d8-8930-443b-8aca-f105eda94416</downstream-id>

#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4313b22768> AOPWiki 2023-06-15T04:45:31

2023-06-15T04:45:31

Increased LCN2/iron complex leading to neurological disorders

Lipocalin 2/Iron complex increases, Cognative dysfunction

Allie Always

Phonethip Phommaly, Korea Institute of Toxicology, Human and Environmental Toxicology, South Korea Huong Giang Le, Korea Institute of Science and Technology, Clean Energy Research Center, South Korea

2.5

Iron accumulation in the brain has been implicated in the development of various neurological disorders, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and multiple sclerosis. In Parkinson's disease, iron accumulation has been observed in the substantia nigra (SN), a region of the brain that is particularly vulnerable to degeneration in this disease. Iron can catalyze the production of reactive oxygen species (ROS) and cause oxidative damage to neurons, which can contribute to neurodegeneration. In Alzheimer's disease, iron accumulation has been observed in the hippocampus and cerebral cortex, regions of the brain that are affected in this disease. Iron can also contribute to the aggregation of beta-amyloid protein, a hallmark feature of Alzheimer's disease. In Huntington's disease, iron accumulation has been observed in the caudate nucleus and putamen, regions of the brain that are affected in this disease. Iron can also contribute to the aggregation of mutant huntingtin protein, which is a key pathological feature of Huntington's disease. In multiple sclerosis, iron accumulation has been observed in lesions in the brain and spinal cord, and may contribute to demyelination and neurodegeneration in this disease. Overall, iron accumulation in the brain can contribute to the development of various neurological disorders through multiple mechanisms, including oxidative stress, protein aggregation, and neuroinflammation.

adjacent

High

Moderate adjacent

High

High adjacent

Low

Moderate

Old Age

Moderate

<div> <table class="table table-bordered table-fullwidth"> <thead> <tr> <th>Modulating Factor (MF)</th> <th>Influence or Outcome</th> <th>KER(s) involved</th> </tr> </thead> <tbody> <tr> <td> </td> <td> </td> <td> </td> </tr> </tbody> </table> </div>

<div style="margin-left:30px; text-align:left"> <div style="margin-left:30px; text-align:left">•Hyatt, G. A., & Dowling, J. E. (1997). Retinoic acid. A key molecule for eye and photoreceptor development. Investigative ophthalmology & visual science, 38(8), 1471-1475.</div> <div style="margin-left:30px; text-align:left">•Marsh-Armstrong, N., McCaffery, P., Gilbert, W., Dowling, J. E., & Dräger, U. C. (1994). Retinoic acid is necessary for development of the ventral retina in zebrafish. Proceedings of the National Academy of Sciences, 91(15), 7286-7290.</div> <div style="margin-left:30px; text-align:left">•Luo, T., Sakai, Y., Wagner, E., & Dräger, U. C. (2006). Retinoids, eye development, and maturation of visual function. Journal of neurobiology, 66(7), 677-686.</div> <div style="margin-left:30px; text-align:left">•Hyatt, G. A., Schmitt, E. A., Marsh-Armstrong, N., McCaffery, P., Drager, U. C., & Dowling, J. E. (1996). Retinoic acid establishes ventral retinal characteristics. Development, 122(1), 195-204.</div> <div style="margin-left:30px; text-align:left">•Kam, R. K. T., Deng, Y., Chen, Y., & Zhao, H. (2012). Retinoic acid synthesis and functions in early embryonic development. Cell & bioscience, 2(1), 11.</div> <div style="margin-left:30px; text-align:left">•Matt, N., Dupé, V., Garnier, J. M., Dennefeld, C., Chambon, P., Mark, M., & Ghyselinck, N. B. (2005). Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Development, 132(21), 4789-4800.</div> <div style="margin-left:30px; text-align:left">•Duester, G. (2009). Keeping an eye on retinoic acid signaling during eye development. Chemico-biological interactions, 178(1-3), 178-181.</div> <div style="margin-left:30px; text-align:left">•Le, H. G. T., Dowling, J. E., & Cameron, D. J. (2012). Early retinoic acid deprivation in developing zebrafish results in microphthalmia. Visual neuroscience, 29(4-5), 219-228.</div> </div> AOPWiki 2023-06-12T05:11:18

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