Abstract:
:Amyotrophic lateral sclerosis (ALS) is a degenerative disease with a progressive loss of motor neurons in the central nervous system (CNS). However, there are unsolved problems with the therapies for this disease. α-Lipoic acid (LA) is a natural, universal antioxidant capable of scavenging hydroxyl radicals as well as regenerating a series of antioxidant enzymes that has been widely used in clinical settings. This study aimed to evaluate the antioxidant and neuroprotective effects of LA in ALS cell and Drosophila models with mutant G85R and G93A hSOD1 genes. The biological effects of LA and the protein levels of several antioxidant factors were examined, as were those of phospho-Akt and phospho-ERK. Furthermore, specific inhibitors of the PI3K/Akt and MEK/ERK signaling pathways were used to analyze their effects on LA-induced antioxidant expression in vivo and in vitro. Evidences showed that the mutant hSOD1 resulted in the increased oxidative stress, abnormal antioxidant signaling and pathological behaviors in motor performance and survival compared with non-mutant hSOD1 models, treatment with LA improved motor activity and survival in transgenic flies, prevented NSC34 cells from mutant hSOD1 or H2O2 induced decreased antioxidant enzymes as well as increased ROS levels. In addition, LA regulated the expression levels of antioxidant proteins in a dose- and periodical time-dependent manner, which might be mediated by ERK/Akt pathway activation and independent from the mutant hSOD1 gene. Our observations suggest that LA exerts strong and positive antioxidant and neuroprotective effects through the activation of the ERK-Akt pathway in hSOD1 ALS models.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
Wang T,Cheng J,Wang S,Wang X,Jiang H,Yang Y,Wang Y,Zhang C,Liang W,Feng Hdoi
10.1016/j.brainresbull.2018.05.019subject
Has Abstractpub_date
2018-06-01 00:00:00pages
299-310eissn
0361-9230issn
1873-2747pii
S0361-9230(18)30169-2journal_volume
140pub_type
杂志文章abstract:OBJECTIVE:Cerebral ischemic stroke (IS) threatens the daily life of individuals, with high mortality. Emerging studies have deciphered the independent roles of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5), microRNA (miR)-455-5p and phosphatase and tensin homolog (PTEN) in IS, but the understanding...
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journal_title:Brain research bulletin
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(89)90057-9
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(84)90153-9
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abstract::The beta-galactosidase protein generated by the bacterial LacZ gene is widely used to map gene expression patterns. The ease of its use is only rivaled by green fluorescent protein, which can be used in combination with various other procedures such as immunocytochemistry, flow cytometry, or tract tracing. The beta-ga...
journal_title:Brain research bulletin
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journal_title:Brain research bulletin
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(90)90074-a
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(94)90135-x
更新日期:1994-01-01 00:00:00
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(95)00008-3
更新日期:1995-01-01 00:00:00
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(89)90112-3
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(79)90106-0
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journal_title:Brain research bulletin
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(96)00004-4
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journal_title:Brain research bulletin
pub_type: 杂志文章
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journal_title:Brain research bulletin
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doi:10.1016/0361-9230(95)00081-o
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(94)90083-3
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(93)90142-x
更新日期:1993-01-01 00:00:00
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(94)00228-s
更新日期:1995-01-01 00:00:00
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(92)90009-m
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abstract::Binary mixtures of acid with salt were observed to produce enhancing effects on oral chemoreceptor responses by recording the activity of the whole glossopharyngeal nerve of the clawed toad (Xenopus laevis). The mixtures of HCl with various inorganic salts elicited responses larger than the sum of the responses to ind...
journal_title:Brain research bulletin
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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journal_title:Brain research bulletin
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(85)90210-2
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abstract::Adult female Zucker lean and obese rats were treated for 14 days with 3.5 nm/kg oleoyl-estrone (OE) in liposomes (Merlin-2) through continuous i.v. injection with osmotic minipumps. Rat wt. and food intake were measured daily. On days 0, 3, 6, 10, and 14, groups of rats were killed and their hypothalamic nuclei [later...
journal_title:Brain research bulletin
pub_type: 杂志文章
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