| Item type |
文献 / Documents(1) |
| 公開日 |
2020-01-24 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.3389/fphar.2018.01311 |
|
|
言語 |
ja |
|
|
関連名称 |
10.3389/fphar.2018.01311 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
c-Abl Inhibition Exerts Symptomatic Antiparkinsonian Effects Through a Striatal Postsynaptic Mechanism |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
c-Abl Inhibition Exerts Antiparkinsonian Effects |
|
言語 |
en |
| 著者 |
Zhou, Yu
ヤマムラ, ユキオ
オガワ, マサトシ
ツジ, リョウスケ
土屋, 浩一郎
笠原, 二郎
後藤, 惠
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Parkinson’s disease (PD) is caused by a progressive degeneration of nigral dopaminergic cells leading to striatal dopamine deficiency. From the perspective of antiparkinsonian drug mechanisms, pharmacologic treatment of PD can be divided into symptomatic and disease-modifying (neuroprotective) therapies. An increase in the level and activity of the Abelson non-receptor tyrosine kinase (c-Abl) has been identified in both human and mouse brains under PD conditions. In the last decade, it has been observed that the inhibition of c-Abl activity holds promise for protection against the degeneration of nigral dopaminergic cells in PD and thereby exerts antiparkinsonian effects. Accordingly, c-Abl inhibitors have been applied clinically as a disease-modifying therapeutic strategy for PD treatment. Moreover, in a series of studies, including that presented here, experimental evidence suggests that in a mouse model of parkinsonism induced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, c-Abl inhibition exerts an immediate effect improving motor impairments by normalizing altered activity in striatal postsynaptic signaling pathways mediated by Cdk5 (cyclin-dependent kinase 5) and DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein 32 kDa). Based on this, we suggest that c-Abl inhibitors represent an ideal antiparkinsonian agent that has both disease-modifying and symptomatic effects. Future research is required to carefully evaluate the therapeutic efficacy and clinical challenges associated with applying c-Abl inhibitors to the treatment of PD. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
c-Abl |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
cyclin-dependent kinase 5 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
DARPP-32 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
parkinsonism |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
striatum |
| 書誌情報 |
en : Frontiers in Pharmacology
巻 9,
p. 1311,
発行日 2018-11-16
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
16639812 |
| 出版者 |
|
|
出版者 |
Frontiers |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2018 Zhou, Yamamura, Ogawa, Tsuji, Tsuchiya, Kasahara and Goto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| EID |
|
|
識別子 |
358014 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
fphar_9_1311.pdf (5.27 MB)
.png)
