Please use this identifier to cite or link to this item:
https://hdl.handle.net/20.500.12540/75
DC Field | Value | Language |
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dc.contributor.author | Wong, Aloysius | en_US |
dc.contributor.author | Lu, Lu | en_US |
dc.contributor.author | Zhang, Changjiang | en_US |
dc.contributor.author | Meng, Yu | en_US |
dc.contributor.author | Michelena, Toby M. | en_US |
dc.date.accessioned | 2020-06-25T06:46:12Z | - |
dc.date.available | 2020-06-25T06:46:12Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Lu, L., Michelena, T. M., Wong, A., Zhang, C. J., & Meng, Y. (2018, July). The inhibition of acetylcholinesterase by a brain-targeting polylysine-ApoE peptide: biochemical and structural characterizations. In 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (pp. 155-158). IEEE. | en_US |
dc.identifier.uri | https://hdl.handle.net/20.500.12540/75 | - |
dc.description | Please note that preprint copy is not available on WIRE. Please contact wire@wku.edu.cn to request an electronic copy of this item. | en_US |
dc.description.abstract | The in-trans delivery of protein therapeutics across the blood-brain barrier by K16ApoE peptide carrier has been demonstrated to improve the neurological symptoms and increase the life-span of late-infantile neuronal ceroid lipofuscinosis (LINCL) mice. However, acute toxicity of K16ApoE was observed in LINCL mice resulting in a narrow therapeutic index, limiting the potential of translating the K16ApoE into a viable drug delivery system. This study aims to unravel the toxic mechanism of action. We hypothesized that the toxic response towards the peptide was induced by inhibition of acetylcholinesterase (AChE) activity at neuro-muscular junction. Here, results from the dose-response study suggested that AChE activity was inhibited by K16ApoE at either low or high doses but not at the mid-dose where a significant increase in AChE activity was observed. Meanwhile, molecular docking simulations showed that the N-terminus of K16ApoE is capable of binding to the active site gorge of AChE. In addition to a favorable spatial orientation, this docking pose also revealed strong surface charge interactions which may account for the observed inhibitory effect. While statistical analysis of the dose response and survival ratio suggested that AChE is not the primary mechanism of action for the acute toxicity of K16ApoE, both biochemical evidence and structural analysis have assigned indirect but critical roles for AChE in the overall toxicity mechanism of this peptide carrier. | en_US |
dc.format.extent | 1 page | en_US |
dc.format.mimetype | application/pdf | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Institute of Electrical and Electronics Engineers (IEEE) | en_US |
dc.relation.ispartof | 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | - |
dc.subject.lcsh | Protein Therapeutics | en_US |
dc.title | The inhibition of acetylcholinesterase by a brain-targeting polylysine-apoE peptide: Biochemical and structural characterizations | en_US |
dc.type | Conference Proceeding | en_US |
dc.rights.license | Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) | en_US |
dc.relation.conference | 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) | en_US |
dc.identifier.doi | 10.1109/EMBC.2018.8512202 | - |
Appears in Collections: | Scholarly Publications |
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Unavailable.pdf | 77.37 kB | Adobe PDF | View/Open |
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