Chronic hyperglycemia impairment of neuron function (Homo sapiens)
From WikiPathways
Description
Chronic excess of glucose (chronic hyperglycemia) impairs neuron function via the polyol pathway, causing ROS and RNS eventually. These activate nuclear transcription factors that increase the expression of ion channel transducers TRP and NaV and impairs their capacity to self-repair. Meanwhile, microglia-released cytokines, ATP, BDNF, and NO stimulate GPCR and tyrosine kinase receptors. This causes a signaling cascade leading to the phosphorylation of TRP and NaV channels, further distorting normal biology.
Quality Tags
Ontology Terms
Bibliography
- Perrone A, Giovino A, Benny J, Martinelli F; ''Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects.''; Oxid Med Cell Longev, 2020 PubMed Europe PMC Scholia
- Rajchgot T, Thomas SC, Wang JC, Ahmadi M, Balood M, Crosson T, Dias JP, Couture R, Claing A, Talbot S; ''Neurons and Microglia; A Sickly-Sweet Duo in Diabetic Pain Neuropathy.''; Front Neurosci, 2019 PubMed Europe PMC Scholia
- King RH; ''The role of glycation in the pathogenesis of diabetic polyneuropathy.''; Mol Pathol, 2001 PubMed Europe PMC Scholia
- Turner DP; ''Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity.''; Cancer Res, 2015 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ADP | Metabolite | Q185253 (Wikidata) | |
AGE | Metabolite | 84123 (ChEBI) | |
ATP | Metabolite | Q80863 (Wikidata) | |
Aldose reductase | Protein | 1.1.1.21 (Enzyme Nomenclature) | |
BDNF-TrkB signaling | Pathway | WP3676 (WikiPathways) | |
BDNF | Protein | 627 (Entrez Gene) | |
BDNFR | Protein | receptor, not specified in publication [PMID: 30766472] which specific one. "BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkB (pronounced "Track B") and the LNGFR (for low-affinity nerve growth factor receptor, also known as p75).[26] It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor." Source: https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor . | |
C3 | Protein | 718 (Entrez Gene) | |
Ca2+ | Metabolite | 29108 (ChEBI) | |
Cytokines | Protein | Q212354 (Wikidata) | |
DNA | Pathway | WP466 (WikiPathways) | |
ETC | Pathway | WP111 (WikiPathways) | Assumed to mean 'Electron Transport Chain' |
Fructose | Metabolite | Q61738075 (Wikidata) | |
GPCR | Protein | Q38173 (Wikidata) | |
Glucose | Metabolite | Q37525 (Wikidata) | |
Glut-1 | Protein | 6513 (Entrez Gene) | |
Glut-3 | Protein | 6515 (Entrez Gene) | |
INOS | Protein | P35228 (Uniprot-TrEMBL) | Assumed to represent one of the nitric oxide sunthases (due to connection to NO metabolite); the xNOS family of enzymes catalyzes the production of nitric oxide from L-arginine. Publication [PMID: 30766472] states :"Nitric oxide (NO) is a potent vasoactive gas formed by three nitric oxide synthase (NOS) isoenzymes: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS)" |
Ion imbalance | |||
K+ | Metabolite | 29103 (ChEBI) | |
MMP10 | GeneProduct | 4319 (Entrez Gene) | |
MMP11 | GeneProduct | 4320 (Entrez Gene) | |
MMP12 | GeneProduct | 4321 (Entrez Gene) | |
MMP13 | GeneProduct | 4322 (Entrez Gene) | |
MMP1 | GeneProduct | 4312 (Entrez Gene) | |
MMP14 | GeneProduct | 4323 (Entrez Gene) | |
MMP15 | GeneProduct | 4324 (Entrez Gene) | |
MMP16 | GeneProduct | 4325 (Entrez Gene) | |
MMP17 | GeneProduct | 4326 (Entrez Gene) | |
MMP19 | GeneProduct | 4327 (Entrez Gene) | |
MMP20 | GeneProduct | 9313 (Entrez Gene) | |
MMP21 | GeneProduct | 118856 (Entrez Gene) | |
MMP23B | GeneProduct | 8510 (Entrez Gene) | |
MMP24 | GeneProduct | 10893 (Entrez Gene) | |
MMP2 | GeneProduct | 4313 (Entrez Gene) | |
MMP25 | GeneProduct | 64386 (Entrez Gene) | |
MMP27 | GeneProduct | 64066 (Entrez Gene) | |
MMP28 | GeneProduct | 79148 (Entrez Gene) | |
MMP3 | GeneProduct | 4314 (Entrez Gene) | |
MMP7 | GeneProduct | 4316 (Entrez Gene) | |
MMP8 | GeneProduct | 4317 (Entrez Gene) | |
MMP9 | GeneProduct | 4318 (Entrez Gene) | |
NADH | Metabolite | Q26987453 (Wikidata) | |
NADPH oxidase | Protein | Q97651124 (Wikidata) | |
NADPH | Metabolite | Q26841327 (Wikidata) | |
NADP | Metabolite | Q26987754 (Wikidata) | |
NAD | Metabolite | Q12499775 (Wikidata) | |
NMDA | Protein | IPR018882 (InterPro) | "increasing N-Methyl-D-Aspartate receptor (NMDAR) phosphorylation reduces its endogenous blockade by magnesium, thereby enhancing calcium (Ca+2) and sodium (Na+) influx" [PMID: 30766472]. Receptor exist in 8 variants. |
NO | Metabolite | 16480 (ChEBI) | |
NRS | Metabolite | Probably Nitrate reductases (NRs); in publication [PMID: 30766472] mentioned as "iNOS-NO-NRS axis, activated microglia are a major source of free radicals in the spinal cords of animals with DPN"; might need to be captured as a Protein, EC code: 1.7.99.4 | |
Na+ | Metabolite | Q31541104 (Wikidata) | |
Nav1.6 | Protein | ENSG00000196876 (Ensembl) | |
Nav1.7 | Protein | ENSG00000169432 (Ensembl) | |
Nav1.8 | Protein | ENSG00000185313 (Ensembl) | |
Na⁺/K⁺-ATPase | Protein | 7.2.2.13 (Enzyme Nomenclature) | aka sodium–potassium pump |
O2- radical | Metabolite | 61073 (ChEBI) | |
PGE2 | Metabolite | Q416554 (Wikidata) | |
PKC | Protein | ||
PKC | Protein | 2.7.11.13 (Enzyme Nomenclature) | Assumed to represent Protein kinase C, a family of protein kinases. |
PRKCA | GeneProduct | 5578 (Entrez Gene) | |
PRKCB | GeneProduct | 5579 (Entrez Gene) | |
PRKCD | GeneProduct | 5580 (Entrez Gene) | |
PRKCE | GeneProduct | 5581 (Entrez Gene) | |
PRKCG | GeneProduct | 5582 (Entrez Gene) | |
PRKCH | GeneProduct | 5583 (Entrez Gene) | |
PRKCI | GeneProduct | 5584 (Entrez Gene) | |
PRKCQ | GeneProduct | 5588 (Entrez Gene) | |
PRKCZ | GeneProduct | 5590 (Entrez Gene) | |
PRKD3 | GeneProduct | 23683 (Entrez Gene) | |
Protein kinases | Protein | ||
Protein synthesis | Pathway | WP1812 (WikiPathways) | |
RAGE | Protein | 177 (Entrez Gene) | Also AGER |
ROS | Metabolite | 26523 (ChEBI) | |
SNAP25 | GeneProduct | 6616 (Entrez Gene) | |
Sensitization and hyperexcitation | Pathway | ||
Sorbitol dehydrogenase | Protein | Q00796 (Uniprot-TrEMBL) | |
Sorbitol | Metabolite | Q245280 (Wikidata) | |
TKR | Protein | ENSG00000007350 (Ensembl) | Also known as TKTL1 |
TRPA1 | Protein | O75762 (Uniprot-TrEMBL) | AKA transient receptor potential ankyrin-1 |
TRPV1 | Protein | Q8NER1 (Uniprot-TrEMBL) | AKA transient receptor potential vannilloid-1 |
Urea cycle | Pathway | WP4595 (WikiPathways) | |
e- | Metabolite | 10545 (ChEBI) |
Annotated Interactions
Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
Sorbitol | Fructose | mim-conversion | 33033 (Rhea) |