Abstract：
:The development of neuroprotective agents is necessary for the treatment of neurodegenerative diseases. Here, we report PQA-11, a prenylated quinolinecarboxylic acid (PQA) derivative, as a potent neuroprotectant. PQA-11 inhibits glutamate-induced cell death and caspase-3 activation in hippocampal cultures, as well as inhibits N-Methyl-4-phenylpyridinium iodide- and amyloid β1-42-induced cell death in SH-SY5Y cells. PQA-11 also suppresses mitogen-activated protein kinase kinase 4 (MKK4) and c-jun N-terminal kinase (JNK) signaling activated by these neurotoxins. Quartz crystal microbalance analysis and in vitro kinase assay reveal that PQA-11 interacts with MKK4, and inhibits its sphingosine-induced activation. The administration of PQA-11 by intraperitoneal injection alleviates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of nigrostriatal dopaminergic neurons in mice. These results suggest that PQA-11 is a unique MKK4 inhibitor with potent neuroprotective effects in vitro and in vivo. PQA-11 may be a valuable lead for the development of novel neuroprotectants.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Ogura M,Kikuchi H,Shakespear N,Suzuki T,Yamaki J,Homma MK,Oshima Y,Homma Ydoi
10.1016/j.bcp.2018.10.008subject
Has Abstractpub_date
2019-04-01 00:00:00pages
109-122eissn
0006-2952issn
1873-2968pii
S0006-2952(18)30429-5journal_volume
162pub_type
杂志文章abstract：:Incorporation of thia fatty acids and their effects on the fatty acid composition in phospholipids has been investigated in 7800 C1 hepatoma cells and cultured hepatocytes. 3-Thia fatty acids of chain lengths from dodecyl-to hexadecyl-thioacetic acid were incorporated into phospholipids during a 3-day incubation. Long...
journal_title：Biochemical pharmacology
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doi：10.1016/0006-2952(95)02182-5
更新日期：1996-03-22 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90737-x
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/0006-2952(91)90112-i
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doi：10.1016/j.bcp.2009.12.012
更新日期：2010-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：2010-07-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(94)00455-u
更新日期：1995-03-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90315-n
更新日期：1993-04-22 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00483-8
更新日期：1998-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00226-8
更新日期：1997-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.02.025
更新日期：2014-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90573-9
更新日期：1987-12-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90411-4
更新日期：1987-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00265-2
更新日期：1995-10-12 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(89)90231-1
更新日期：1989-03-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1990-06-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2005-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2008-12-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90109-1
更新日期：1985-01-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00125-2
更新日期：1999-08-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2005.11.006
更新日期：2006-03-30 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.05.004
更新日期：2009-09-01 00:00:00
