ChristianJoel
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Inscrit le: 25 Déc 2019
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Mer Déc 25, 2019 2:44 am |
 
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The finding that PcTx1 and ASIC1 asics gel lyte antisense oligo-deoxynucleotides infused into the intrathecal space both had analgesic effects further suggests a role for ASIC1 in the central mediation of pain ( 108 , 272 ). Moreover, recently defined interactions between ASICs and peptides found within the CNS, such as the dynorphins, reinforce the possibility that CNS ASICs may be manipulated to manage pain ( 347 , 426 ).
Studies of ASIC1 in mice have implicated it in synaptic plasticity, learning, and memory formation (409 411). In the CNS, the protein appears to localize with the postsynaptic density-95 protein (PSD-95), which likely targets ASIC1 to areas of high synaptic density ( 409 , 410 ). Behavioral tests of mice overexpressing ASIC1 found increased acquired fear related behavior ( 411 ), while ASIC1 knockout mice showed a deficit in cued and contextual fear conditioning ( 409 ), suggesting that perhaps ASIC1 could play asics gel nimbus a role in anxiety or fear learning. Interestingly, it has recently been reported that decreased brain pH resulting from hypercarbia also elicits fear in mice, a behavioral response that is attenuated by ASIC1 knockout ( 442 ).
However, a case-control twin study showed no association between polymorphisms of ASIC1 asics tigers and anxiety spectrum disorders ( 175 ). Still, functional tests with ASIC inhibitors in animal models found that ASIC inhibition was able to produce antidepressive, sedative, and anxiolytic effects ( 88 , 112 , 234 ). For example, amiloride, PcTx1, and A317567 all exhibited anxiolytic activity, with PcTx1 and A317567 being most effective, most likely reflecting the lower potency of amiloride in ASIC inhibition ( 112 ). The exact role and mechanism of ASIC in anxiety and fear learning remains to be elucidated, but the data suggest that inhibition of ASICs can play a role in the treatment of asics trainers mens anxiety or depression states.
The involvement of ASICs in Parkinson's disease is a relatively recent development. Parkinson's disease is associated with neuronal degeneration, loss of dopaminergic neurons in the substantia nigra, and acidosis ( 51 ). In a mouse model of Parkinson's disease, pretreatment of animals with amiloride or crude psalmotoxin venom prevented loss of dopaminergic neurons due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration ( 14 ). The effects of amiloride were comparable to those seen for other compounds capable of preserving dopaminergic neurons in the MPTP model.
These results suggest the involvement of ASIC1 in neuronal loss, but the relative nonspecificity of the agents used suggests that these data should be interpreted with caution. However, a role for ASIC2a in Parkinson's disease has emerged from studies of parkin , an E3 ubiquitin ligase that is mutated in genetically related autosomal recessive Parkinson's disease. One target of parkin appears to be PICK1 (protein interacting with C kinase 1), a protein that binds to the COOH-terminal PDZ motif of ASIC1 and ASIC2 ( 110 , 182 ), and which potentiates ASIC-related currents ( 31 , 184 ).
Touch sensation also involves ASICs, although the exact role of the different channels asics womens running shoes is still somewhat unclear. Pacinian corpuscles express ASIC1 and 2 in humans ( 62 ), although loss of ASIC1 expression did not appear to affect touch sensation in mice ( 294 ). In contrast, ASIC3 has been suggested to be the important mediator of touch sensation in mice ( 315 ).One of the major pathologies for which a potential role of ASICs and ENaCs is currently emerging is cancer. Multiple studies have shown that ASICs and ENaCs are associated with cell migration and proliferation, even in nontumor cells ( 48 [img]http://www.ducortelephone.com/images/k/asics womens running shoes-694dpy.jpg[/img] , 83 , 97 , 155 , 156 ). |
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