| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000433925 |
| 005 | | 20200226134139 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781088385371 |
| 035 | |
▼a (MiAaPQ)AAI22615989 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 620.5 |
| 100 | 1 |
▼a Yeh, Chung-Yang. |
| 245 | 10 |
▼a Targeting Kv2.1/Syntaxin Interaction for Neuroprotection. |
| 260 | |
▼a [S.l.]:
▼b University of Pittsburgh.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 157 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B. |
| 500 | |
▼a Includes supplementary digital materials. |
| 500 | |
▼a Advisor: Aizenman, Elias |
| 502 | 1 |
▼a Thesis (Ph.D.)--University of Pittsburgh, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a The regulation of cytosolic potassium is a convergent factor in cell death programs of many mammalian cell types including central nervous system neurons. Physiological levels of potassium concentrations can suppress the activation of critical caspases and nucleases necessary for cell death. Under physiological conditions, several ion channels and exchangers sustain intracellular potassium levels. Conversely, tightly regulated molecular pathways facilitate the depletion of intracellular potassium after injury to very low concentrations, enabling cell death mechanisms to proceed. Several research groups have shown that preventing the loss of intracellular potassium after injury through various approaches can increase the survivability of several cell types. In neurons, the main regulator of intracellular potassium after injury is the delayed rectifier potassium channel Kv2.1. Strategies aimed to ameliorate Kv2.1-dependent neuronal cell death have been investigated over the past several years. We have come to understand that lethal oxidative damage set forth unique, zinc-dependent phosphorylation of Kv2.1, leading to enhanced membrane channel insertion and elevated potassium efflux currents. Critical to this pathway is the protein-protein interaction between Kv2.1 and the cell surface soluble NSF attachment protein receptor (SNARE) syntaxin 1A (syntaxin). Interrupting this interaction has been shown to improve neuronal survival in vitro. In this dissertation, I report several studies that further clarify the molecular interactions between Kv2.1 and syntaxin, and provide the first in vivo evidence that disrupting the Kv2.1-syntaxin binding is a viable neuroprotective strategy. We explored several approaches using both peptide-based and synthetic small molecules as the protective agent. To cap off these findings, I provide preliminary data that leverages the hepatitis virus protein NS5A to suppress Kv2.1-dependent cell death in ischemic stroke. We intend for the work presented here to serve as the basis to further unravel the role of Kv2.1 in other neurodegenerative conditions and eventually make the translational leap to improve clinical treatments. |
| 590 | |
▼a School code: 0178. |
| 650 | 4 |
▼a Nanoscience. |
| 690 | |
▼a 0565 |
| 710 | 20 |
▼a University of Pittsburgh.
▼b School of Medicine. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-03B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0178 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15493349
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |