Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acoustic trauma is well known to cause peripheral damage with subsequent effects in the central auditory system. The inferior colliculus (IC) is a major auditory center for the integration of ascending and descending information and is involved in noise-induced tinnitus and central hyperactivity. Here we show that the early effects of acoustic trauma, that eventually result in permanent damage to auditory system, lead to a transient activation of BDNF and mitogen-activated protein kinases (MAPK) including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the IC. In contrast, the early effects of acoustic trauma that result in a temporary damage produced a reversible activation only of p38. The transient activation of MAPK and BDNF in the IC after permanent acoustic trauma is attributed to the plastic changes triggered by a decreased signal input from the damaged periphery. The pattern of MAPK and BDNF activation in the IC is different from that previously described for the cochlea from this laboratory. The differences in the pattern of MAPK and BDNF expression in the IC highlight unique molecular mechanisms underlying temporary and permanent acoustic damage to the central auditory system.
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PMID:The expression of mitogen-activated protein kinases and brain-derived neurotrophic factor in inferior colliculi after acoustic trauma. 2059 95

Aminoglycosides, cisplatin, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used pharmacological agents. There is a possibility, however, that the use of these agents may induce transient or permanent hearing loss and tinnitus as side effects. Recent animal studies have clarified mechanisms leading to the ototoxicity induced by these agents, at least in part. The permanent hearing loss caused by aminoglycosides and cisplatin is suggested to be predominantly associated with the apoptotic death of outer hair cells. Both drugs generate reactive oxygen species (ROS) in the inner ear. ROS can activate cell-death pathways such as the c-Jun Nterminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways, which in turn, induce hair cell apoptosis. On the other hand, the abuse of NSAIDs may transiently cause tinnitus and mild to moderate hearing loss. NSAIDs impair the active process of the outer hair cells and affect peripheral and central auditory neurons. Conversely, recent reports clarified that NSAIDs are potential therapeutic agents against cochlear injuries. In this review, recent findings from animal studies regarding the ototoxicity induced by aminoglycosides, cisplatin, and NSAIDs are summarized. Their ototoxic mechanisms are focused on.
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PMID:Ototoxicity: mechanisms of cochlear impairment and its prevention. 2191 41

Vestibular schwannomas (VS), benign intracranial tumors originating from the vestibulocochlear nerve, usually present with hearing loss, tinnitus, and balance dysfunction. Rarely, however, if untreated, these neoplasms can cause significant patient compromise - resulting in facial paralysis, brainstem compression, and even death. Those with vestibular schwannomas currently choose between surgery and stereotactic radiation therapy as available treatment options. Unfortunately, no medical therapies are presently U.S. Food & Drug Administration approved, representing an urgent and unmet clinical need. Recent breakthroughs in research have discovered key cell surface receptors and intracellular signaling pathways that drive vestibular schwannoma tumorigenesis, proliferation, and survival. A number of promising inhibitors targeting these signaling molecules have also now shown efficacy in preclinical VS cell culture models and animal experiments, with some recently entering human clinical trials. In this review, we summarize ErbB receptor signaling, PDGF receptors, MAP kinase signaling, AKT, p21-activated kinase signaling, mTOR, and VEGF signaling in the context of vestibular schwannoma drug development efforts worldwide. Today, it is truly an exciting time as our specialty stands on the verge of major breakthroughs in the development of medical therapies for VS.
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PMID:Molecular pathogenesis of vestibular schwannomas: insights for the development of novel medical therapies. 2250 Apr 97