Peptides
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Septic encephalopathy is frequently diagnosed in critically ill patients and in up to 70% of patients with severe systemic infection [19]. The syndrome is defined by diffuse cerebral dysfunction or structural abnormalities attributed to the effects of systemic infection, rather than a direct central nervous system cause. ⋯ Sepsis survivors present long term cognitive impairment, including alterations of memory, attention and concentration [10,54]. Here, we propose that neuropeptides may play a key role in septic encephalopathy, leading to a vicious circle characterized by brain disease and systemic inflammation.
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The spider venom peptide Huwentoxin-IV (HwTx-IV) 1 is a potent antagonist of hNav1.7 (IC50 determined herein as 17 ± 2 nM). Nav1.7 is a voltage-gated sodium channel involved in the generation and conduction of neuropathic and nociceptive pain signals. ⋯ In particular, the native residues Glu(1), Glu(4), Phe(6) and Tyr(33) were revealed as important activity modulators and several peptides bearing mutations in these positions showed significantly increased potency on hNav1.7 while maintaining the original selectivity profile of the wild-type peptide 1 on hNav1.5. Peptide 47 (Gly(1), Gly(4), Trp(33)-HwTx) demonstrated the largest potency increase on hNav1.7 (IC50 0.4 ± 0.1 nM).