Abstract：
:The activity of beta-secretase (BACE1), the endo-protease essential for the production of amyloid beta (Abeta) peptides, is increased in brain of late-onset sporadic Alzheimer's disease (AD), and oxidative stress is the potential cause of this event. Oxidative stress up-regulates the expression and the activity of BACE1 in cellular and animal models, through a mechanism that involves the increase of gamma-secretase cleavage on APP and the activation of c-jun N-terminal kinase/activator protein 1 (JNK/AP1) pathway. We further characterized the cellular pathways that control BACE1 expression under oxidative stress. We investigated the involvement of extracellular signal regulated MAP kinase (ERK1/2) pathway in the regulation of BACE1 expression, since it has been recently shown that ERK1/2 is an endogenous regulator of the gamma-secretase activity. We found that ERK1/2 pathway negatively modulates BACE1 expression and activity. Moreover, we observed that conditions that abrogate the gamma-secretase activity favor the activation of signalling pathways that promote cell survival, such as ERK1/2 and the serine/threonine kinase Akt/protein kinase B (Akt). These data suggest that the positive or negative cellular responses to oxidative stress parallel the activities of the beta- and the gamma-secretase. ERK1/2 and JNK pathways are involved in this bipartite response, which can lead to neurodegeneration or neuroprotection depending on the cellular and environmental conditions or cooperation with other signalling pathways such as Akt cascade.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Tamagno E,Guglielmotto M,Giliberto L,Vitali A,Borghi R,Autelli R,Danni O,Tabaton Mdoi
10.1016/j.neurobiolaging.2007.12.015subject
Has Abstractpub_date
2009-10-01 00:00:00pages
1563-73issue
10eissn
0197-4580issn
1558-1497pii
S0197-4580(07)00494-0journal_volume
30pub_type
杂志文章abstract：:Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain diseas...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
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doi：10.1016/j.neurobiolaging.2011.09.012
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：1991-05-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.09.019
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.12.009
更新日期：2006-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.01.020
更新日期：2019-05-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.05.016
更新日期：2009-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.020
更新日期：2006-05-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.12.012
更新日期：2020-04-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00012-2
更新日期：1997-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.10.021
更新日期：2012-05-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.09.031
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.04.010
更新日期：2014-10-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章,多中心研究
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更新日期：2007-04-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
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更新日期：2006-01-01 00:00:00
abstract：:Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease caused by an abnormal expansion of a tandem CAG repeat in exon 1 of the androgen receptor (AR) gene that results in an abnormally long polyglutamine tract (polyQ) in the AR protein. As a result, the mutant AR (ARpolyQ) misfolds, forming cytopl...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.05.026
更新日期：2013-11-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.11.014
更新日期：2015-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.10.017
更新日期：2011-10-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disease and is caused by an accumulation of A beta plaque deposits in the brains. Evidence is increasing that green tea flavonoids can protect cells from A beta-mediated neurotoxicity. However, the underlying mechanism remains unclear. Here, we used a human...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.05.012
更新日期：2009-01-01 00:00:00
abstract：:Previous electrophysiological studies in aged rats have revealed a number of deficits in noradrenergic neurotransmission in the central nervous system. Such deficits include subsensitivity to the depressant effects of norepinephrine on cerebellar Purkinje neurons, which has been attributed specifically to altered beta...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(90)90022-r
更新日期：1990-11-01 00:00:00
abstract：:Aged rats show decrements in performance on cognitive tasks that require the use of spatial learning and memory. We used the 8-arm radial water maze (RAWM) to measure spatial learning as a function of age in young (6 months) and old (21 months) male F344 rats. Rats were placed in the RAWM in different start arms with ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(03)00041-1
更新日期：2004-02-01 00:00:00
abstract：OBJECTIVE:We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD:Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2004.03.003
更新日期：2005-02-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 pat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2017-05-01 00:00:00
