Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurologic complications are common after solid organ transplantation and are associated with significant morbidity. Approximately one-third of transplant recipients experiences neurologic alterations with incidence ranging from 10% to 59%. The complications can be divided into such of those common to all types of transplant and others of those specific to transplanted organ. The most common complication seen with all types of transplanted organ is neurotoxicity attributable to immunosuppressive drugs, followed by seizures, opportunistic central nervous system (CNS) infections, cardiovascular events, encephalopathy and de novo CNS neoplasms. Amongst immunosuppressants, calcineurin inhibitors are the main drugs involved in neurotoxicity, leading to complications which ranges from mild symptoms, such as tremors and paresthesia to severe symptoms, such as disabling pain syndrome and leukoencephalopathy. Neurologic complications of liver transplantation are more common than that of other solid organ transplants (13-47%); encephalopathy is the most common CNS complication, followed by seizures; however, central pontine myelinolysis can appear in 1-8% of the patients leading to permanent disabilities or death. In kidney transplanted patients, stroke is the most common neurologic complication, whereas cerebral infarction and bleeding are more typical after heart transplantation. Metabolic, electrolyte and infectious anomalies represent common risk factors; however, identification of specific causes and early diagnosis are still difficult, because of patient's poor clinical status and concomitant systemic and metabolic disorders, which may obscure symptoms.
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PMID:Neurologic complications after solid organ transplantation. 1907 32

TRESK (TWIK-related spinal cord K(+) channel, KCNK18) belongs to the two-pore domain (K2P) background (leak) potassium channel family. Unlike other K2P channels, TRESK is activated by the calcium signal in heterologous expression systems. The activation is mediated by the calcium/calmodulin-dependent protein phosphatase, calcineurin. TRESK is abundantly expressed in dorsal root and trigeminal ganglia. The active ingredient of Sichuan pepper, sanshool, has been suggested to evoke tingling paresthesia by inhibiting the channel in a mechanoreceptor subpopulation of sensory neurons. Recently, dominant-negative mutation of human TRESK was found to be linked to migraine with aura in a large pedigree. It is hoped that future TRESK agonists may prevent or ameliorate the debilitating symptoms of migraine. It will be interesting to see whether the calcineurin-activated K(+) channel maintains normal excitability in the cerebral cortex thereby arresting cortical spreading depression (CSD), or prevents migraine attack only in the trigeminovascular (TGVS) system.
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PMID:TRESK: the lone ranger of two-pore domain potassium channels. 2211 60

The calcineurin inhibitors cyclosporine and tacrolimus are used for their immunosuppressive effects. Neurotoxic side effects include tremor, paresthesia, and headache. Rarer neurotoxicities include seizure, posterior reversible encephalopathy syndrome, and encephalopathy. Tacrolimus tends to be more neurotoxic than cyclosporine. Management of toxicities associated with calcineurin inhibitors includes dose reduction, switching between calcineurin inhibitors, or switching to a calcineurin-free regimen. Tumor necrosis factor (TNF) inhibitors are used in autoimmune diseases. Management of demyelinating conditions among patients treated with anti-TNF should follow standard of care and withdrawal of the anti-TNF. This drug class should be avoided in patients with a history of demyelinating conditions.
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PMID:Neurologic Toxicities Associated with Tumor Necrosis Factor Inhibitors and Calcineurin Inhibitors. 3304 Aug 70