Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paraneoplastic cerebellar degeneration (PCD) is a rare complication of systemic cancer. PCD may present as a "pure", severe pan-cerebellar syndrome of subacute progression or be only one clinical feature in the setting of extensive CNS disease. The most characteristic form of "pure" PCD is associated with the presence of an anti-Purkinje cell antibody (AB), called anti-Yo, in patients with breast or ovarian cancer. The primary tumor is very often unknown when the cerebellar signs occur, and extensive investigations, including laparotomy or prolonged follow-up may be required to demonstrate its presence. More rarely, others AB than anti-Yo are discovered during PCD. Almost 50% of patients with "pure" PCD do not have circulating anti-neuronal AB. In the cases, the primary cancer is more often known and the clinical course of the cerebellar syndrome may be slower. Cerebellar degeneration may also occur during paraneoplastic encephalomyelitis. In this setting, the cerebellar signs which may be isolated at the onset, become associated with other signs of neuraxis involvement (limbic encephalitis, brainstem encephalitis, myelitis and particularly, subacute sensory neuronopathy) during the course of the disease. When a paraneoplastic encephalomyelitis is associated with a small cell lung cancer, an antineuronal AB called anti-Hu is frequently found. Finally PCD may be associated with the opsoclonus-myoclonus syndrome with the Lambert-Eaton syndrome.
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PMID:[Paraneoplastic cerebellar degeneration]. 786 50

Human kallikrein-related peptidase 6 (KLK6) is a member of the kallikrein family of serine-type proteases, characterized as an arginine-specific digestive-type protease capable of degrading a wide-variety of extracellular matrix proteins. KLK6 has been proposed to be a useful biomarker for breast and ovarian cancer prognosis, is abundantly expressed in the CNS and cerebrospinal fluid, and is intimately associated with regions of active inflammatory demyelination in multiple sclerosis (MS) lesions. Inhibition of KLK6 results in delayed onset and reduced severity of symptoms associated with experimental autoimmune encephalomyelitis, suggesting a key effector role for this protease in CNS inflammatory disease. KLK6 has been shown to autolytically cleave internally, leading to inactivation and suggesting a negative feedback inhibition control mechanism. Alternatively, the ability of KLK6 to self-activate has also been reported, suggesting a positive feedback activation loop control mechanism. Activation of pro-KLK6 requires hydrolysis after a Lys residue; however, KLK6 exhibits 2 order of magnitude reduced affinity for hydrolysis after Lys versus Arg residues; therefore, the ability to autolytically activate has been called into question. In the present study the catalytic activity of KLK6 toward its pro-sequence and internal autolytic sequence is characterized. The results show that the ability of KLK6 to activate pro-KLK6 is essentially negligible when compared to the rate of the internal autolytic inactivation or to the ability of other proteases to activate pro-KLK6. The results thus show that the primary autolytic regulatory mechanism of KLK6 is negative feedback inhibition, and activation is likely achieved through the action of a separate protease.
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PMID:The autolytic regulation of human kallikrein-related peptidase 6. 1741 74

Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.
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PMID:OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages. 2682 24