Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sub-acute transmissible spongiform encephalopathies (TSEs) or prion diseases are diseases of little known etiology. The origin of these diseases would appear to be an abnormal protease-resistant prion protein (PrP(res)) which would be infectious by directly inducing its defective conformation to the normal native protein (PrP(C)). This hypothesis does not account for certain aspects of TSEs, such as interference to superinfection: in laboratory animals, inoculation by means of an attenuated strain with a long incubation period protects against later infection by a very virulent strain with a short incubation period. The hypothesis is put forward that there exists a possibility of interference to superinfection between neurodegenerative diseases of unknown origin, thought to be similar to TSEs, and a later infection by a TSE. The study of this interference between bovine spastic paresis (BSP) and bovine spongiform encephalopathy (BSE) could be used as a model for this hypothesis. BSP is a very rare disease among cattle, of unknown etiology; it is curable, in the very early stages, by using tryptophan and especially lithium, potentiated by copper and manganese. An etiology close to that of TSEs has been suggested on several occasions. If interference could be demonstrated between BSP and BSE, interesting data would be provided concerning the etiology, the pathogenesis and possibly the treatment and prevention of these diseases. Notably, such data could lead to the development of a treatment and a prevention with lithium and amino acids precursors of neuromediators (tryptophan, tyrosine, glutamic acid, etc.), as well as the developing of a vaccine to combat TSEs, especially BSE and scrapie.
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PMID:Hypothesis of interference to superinfection between bovine spastic paresis and bovine spongiform encephalopathy; suggestions for experimentation, theoretical and practical interest. 1497 1

Sub-acute transmissible spongiform encephalopathies (TSEs), or prion diseases, are affections in which little is known of their etiology. The predominant theory stipulates that an abnormal protease-resistant prion protein (PrPres) would be infectious by directly inducing its defective conformation to the normal native protein (PrPC). The function of PrPC remains unknown. The preferred localization of PrPC at the level of the synapses supposes a function in neuronal transmission. Several neurotransmitter systems (acetylcholine, GABA, dopamine, etc.) are damaged in TSEs, mainly the serotonin (5-HT) system. At a hypothetical level, PrPC would play a trophic and functional role by regulating the capture of amino acid precursors of neurotransmitters and the functions of neuroreceptors, in particular regarding tryptophan and 5-HT receptors. By comparison with the modes of action of Ras proteins and of the envelope glycoprotein of jaagsiekte sheep retrovirus, the adaptation of an oncogenic model is suggested for the mode of action of PrPres. The sequence of events could be the following: capture of PrPres and forming of an abnormal receptor, chronic disturbance of transduction pathways, more particularly of the phosphatidylinositol-3 kinase (PI-3K)/protein kinase B (Akt)/glycogen synthetase kinase 3 (GSK 3)/Wnt-beta catenin pathway, deregulation of the PrP gene and infrequent and transitory forming of abnormal RNA messengers and, finally, the forming of abnormal proteins and the deterioration of the serotoninergic system. The involvement of endogenous nucleic acids is supposed. The infectious agent of TSEs could be an ancestral form of retrovirus, such as a retrotransposon using the prion protein as an envelope glycoprotein. Pharmacological tests, by comparison with a rare disease of unknown etiology in cattle, bovine spastic paresis, are suggested with the amino acid precursors of neuromediators (tryptophan, tyrosine, glutamic acid, etc.) and with lithium, neuroprotector and regulator of the serotonergic system.
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PMID:Effects on the serotoninergic system in sub-acute transmissible spongiform encephalopathies: current data, hypotheses, suggestions for experimentation. 1578 Apr 84