TABLE 3.
Other proteins.
| Gene | Protein | Function | Function in cochlea | Druggability |
|---|---|---|---|---|
| Neuronal health and protection from oxidative stress | ||||
| JAK1 | Janus Kinase 1 | Tyrosine kinase that phosphorylates STAT proteins, involved in interferon signal transduction | Regulates proliferation in support cells after hair cell death, STAT3 signalling is important during cochlear hair cell differentiation, downregulated by cisplatin treatment | Tclin |
| TGFBR2 | Transforming growth factor receptor 2 | Transmembrane serine/threonine kinase forming withTGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3 | Associated with scarless wound healing, downregulated after electrode insertion (CI-Insertion), and after noise exposure | Tchem |
| CYBB/NOX2 | Cytochromeb-245 heavy chain | Critical component of the membrane-bound oxidase of phagocytes that generates superoxide | Ginkgolide B (reduces NOX2 expression) decreased ROS generation and therefore reduction of cisplatin induced ototoxicity | Tchem |
| TYMP | Thymidine phosphorylase | Reversible phosphorolysis of thymidine, angiogenic factor | Tclin | |
| HMGB1 | High-mobility group box 1 | one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone; involved in immune response, extracellular component: acts as chemokine | May play an important role in cochlea development, possibly influences SGNs’ survival following ototoxic exposure; in stressful conditions liberated from Deiters’ cells to regulate the epithelial reorganization of injured organ of Corti | |
| TIMP1 | Tissue inhibitor of metallo-proteinases | Metalloproteinase inhibitor, also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signalling cascade | early downregulated and subsequent upregulated during sensory cell degeneration. Inhibits MMP, which might participate in cochlear response to acoustic overstimulation and can serve as a novel therapeutic target | Tbio |
| Axonogenesis | ||||
| PTPRS | Protein tyrosine phosphatase receptor type S | Cell surface receptor that binds to glycosaminoglycans, required for normal brain development | involved in primary axonogenesis, and axon guidance during embryogenesis, also implicated in the molecular control of adult nerve repair | Tchem |
| NAMPT | Nicotinamide phosphoribosyl-transferase | Catalyses the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. | Neuroprotective Nampt Inhibitor P7C3 Demonstrates Otoprotection in an Age Related Hearing Loss Model | Tchem |
| UCHL1 | Ubiquitin carboxyl-terminal hydrolase isozyme | involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognises and hydrolyses a peptide bond at the C-terminal glycine of ubiquitin | Downregulated after Gentamycin exposure, Deficiency accelerates Gentamycin-induced ototoxicity | Tchem |
| Otoprotection and cell adhesion molecules | ||||
| GLUL | Glutamine synthetase | Glutamine synthetase that catalyses the ATP-dependent conversion of glutamate and ammonia to glutamine | May function to limit the perilymphatic glutamate concentrations, the most important afferent neurotransmitter in the cochlea | Tchem |
| CEACAM16 | Carcino-embryonic antigen-related cell adhesion molecule 16 | secreted glycoprotein, adhesion protein | Interacts with TECTA. May have a role in connecting stereocilia with the tectorial membrane. Required for proper hearing over an extended frequency range, it may play a role in maintaining the integrity of the tectorial membrane | Tbio |
| CKM | Creatine kinase M-type | Reversibly catalyses the transfer of phosphate between ATP and various phosphogens | Considered to supply ATP for the Na,K-ATPase that mediates the high KCl of endolymph | Tbio |
| Potassium transport and regulation | ||||
| CA3 | Carbonic anhydrase | Reversible hydration of carbon dioxide | Facilitates mitochondrial ATP synthesis and detoxifying free radicals resulting from ATP synthesis, mediates HCO3− secretion into the endolymph, effects the endocochlear potential | Tclin |
| IDH1 | Isocitrate dehydrogenase 1 | Catalyses the oxidative decarboxylation of isocitrate to 2-oxoglutarate | Participates in K+ transport, protects inner ear from oxidative stress during k*recycling, downregulated in age related hearing loss and lead exposure | Tclin |