---
_id: '6198'
abstract:
- lang: eng
  text: 'Stroke is a major public health problem leading to high rates of death and
    disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors
    (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are
    crucial for neuronal injury after stroke insult. However, directly inhibiting
    NMDARs or nNOS can cause severe side effects because they have key physiological
    functions in the CNS. Here we show that cerebral ischemia induces the interaction
    of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95
    interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS
    (nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic
    damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series
    of compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95 interaction,
    ZL006. This drug blocked the ischemia-induced nNOS-PSD-95 association selectively,
    had potent neuroprotective activity in vitro and ameliorated focal cerebral ischemic
    damage in mice and rats subjected to middle cerebral artery occlusion (MCAO) and
    reperfusion. Moreover, it readily crossed the blood-brain barrier, did not inhibit
    NMDAR function, catalytic activity of nNOS or spatial memory, and had no effect
    on aggressive behaviors. Thus, this new drug may serve as a treatment for stroke,
    perhaps without major side effects. '
author:
- first_name: L
  full_name: Zhou, L
  last_name: Zhou
- first_name: F
  full_name: Li, F
  last_name: Li
- first_name: Haibing
  full_name: Xu, Haibing
  id: 310349D0-F248-11E8-B48F-1D18A9856A87
  last_name: Xu
- first_name: CX
  full_name: Luo, CX
  last_name: Luo
- first_name: HY
  full_name: Wu, HY
  last_name: Wu
- first_name: MM
  full_name: Zhu, MM
  last_name: Zhu
- first_name: W
  full_name: Lu, W
  last_name: Lu
- first_name: X
  full_name: Ji, X
  last_name: Ji
- first_name: QG
  full_name: Zhou, QG
  last_name: Zhou
- first_name: DY
  full_name: Zhu, DY
  last_name: Zhu
citation:
  ama: Zhou L, Li F, Xu H, et al. Treatment of cerebral ischemia by disrupting ischemia-induced
    interaction of nNOS with PSD-95. <i>Nature Medicine</i>. 2010;16(12):1439-1443.
    doi:<a href="https://doi.org/10.1038/nm.2245">10.1038/nm.2245</a>
  apa: Zhou, L., Li, F., Xu, H., Luo, C., Wu, H., Zhu, M., … Zhu, D. (2010). Treatment
    of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95.
    <i>Nature Medicine</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/nm.2245">https://doi.org/10.1038/nm.2245</a>
  chicago: Zhou, L, F Li, Haibing Xu, CX Luo, HY Wu, MM Zhu, W Lu, X Ji, QG Zhou,
    and DY Zhu. “Treatment of Cerebral Ischemia by Disrupting Ischemia-Induced Interaction
    of NNOS with PSD-95.” <i>Nature Medicine</i>. Nature Publishing Group, 2010. <a
    href="https://doi.org/10.1038/nm.2245">https://doi.org/10.1038/nm.2245</a>.
  ieee: L. Zhou <i>et al.</i>, “Treatment of cerebral ischemia by disrupting ischemia-induced
    interaction of nNOS with PSD-95,” <i>Nature Medicine</i>, vol. 16, no. 12. Nature
    Publishing Group, pp. 1439–1443, 2010.
  ista: Zhou L, Li F, Xu H, Luo C, Wu H, Zhu M, Lu W, Ji X, Zhou Q, Zhu D. 2010. Treatment
    of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95.
    Nature Medicine. 16(12), 1439–1443.
  mla: Zhou, L., et al. “Treatment of Cerebral Ischemia by Disrupting Ischemia-Induced
    Interaction of NNOS with PSD-95.” <i>Nature Medicine</i>, vol. 16, no. 12, Nature
    Publishing Group, 2010, pp. 1439–43, doi:<a href="https://doi.org/10.1038/nm.2245">10.1038/nm.2245</a>.
  short: L. Zhou, F. Li, H. Xu, C. Luo, H. Wu, M. Zhu, W. Lu, X. Ji, Q. Zhou, D. Zhu,
    Nature Medicine 16 (2010) 1439–1443.
date_created: 2019-04-04T14:55:32Z
date_published: 2010-11-21T00:00:00Z
date_updated: 2021-01-12T08:06:43Z
day: '21'
doi: 10.1038/nm.2245
extern: '1'
external_id:
  pmid:
  - '21102461'
intvolume: '        16'
issue: '12'
language:
- iso: eng
month: '11'
oa_version: None
page: 1439-1443
pmid: 1
publication: Nature Medicine
publication_identifier:
  issn:
  - 1078-8956
  - 1546-170x
publication_status: published
publisher: Nature Publishing Group
quality_controlled: '1'
status: public
title: Treatment of cerebral ischemia by disrupting ischemia-induced interaction of
  nNOS with PSD-95
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2010'
...