Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons exposed to oxidative stress

Tamagno, Elena; Guglielmotto, Michela; Bardini, Paola; Santoro, G; Davit, Annalisa; Simone, D Di; Danni, Oliviero; Tabaton, Massimo

doi:10.1016/s0969-9961(03)00131-1

Cited by 46 publications

(43 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We and others have shown that the expression and activity of BACE1 is increased by oxidant agents (Tamagno et al 2002;Tamagno et al 2003;Tamagno et al 2005;Kao et al 2004;Tong et al 2005). Several reports show that levels of BACE1 protein and activity are increased in brain of sporadic AD patients, compared to Fig.…”

Section: Ab Production Is a Major Link Between Oxidative Stress And Pmentioning

confidence: 83%

“…First, we have shown that oxidant agents and HNE significantly increase the expression, protein levels, and activity of BACE1 in NT2 neurons (Tamagno et al 2002;Tamagno et al 2003). These events are followed by both an overproduction of Ab peptides and morphological signs of apoptotic cell death (Tamagno et al 2005).…”

Section: Ab Production Is a Major Link Between Oxidative Stress And Pmentioning

confidence: 97%

See 1 more Smart Citation

Amyloid-β Production: Major Link Between Oxidative Stress and BACE1

et al. 2011

View full text Add to dashboard Cite

Sequential endoproteolytic cleavages operated by the c-secretase and the b-secretase (BACE1) on the b-amyloid precursor protein result in the production of the b-amyloid (Ab) species, with two C-terminal variants, at residue 40 or at residue 42. Accumulation in brain tissue of aggregates of Ab42 is the major pathogenetic event in Alzheimer's disease (AD). The causes of Ab accumulation in the common sporadic form of AD are not completely understood, but they are likely to include oxidative stress (OS). Data reviewed here shed light on how Ab generation, oxidative stress, and secretase functions are intimately related in sporadic AD. According to our hypothesis, in sporadic AD, OS resulted from several cellular insults such as aging, hypoxia, hyperglycemia, and hypercholesterolemia-that are well-known risk factors for AD development-can determine a primary induction of c-secretase and BACE1. The loop proceeds with the generation of Ab42 and its signaling to BACE1 transcription.

show abstract

Section: Ab Production Is a Major Link Between Oxidative Stress And Pmentioning

confidence: 83%

Section: Ab Production Is a Major Link Between Oxidative Stress And Pmentioning

confidence: 97%

Amyloid-β Production: Major Link Between Oxidative Stress and BACE1

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Recent reports that oxidative stress elevates BACE1 levels in cultured neurons (Tamagno et al, 2002(Tamagno et al, , 2003) support a potential role for ROS in the BACE1 increase in SAD. Similar mechanisms are likely to operate in diseases of other tissues, such as renal failure, in which chronic hypoperfusion of the kidney as a result of atherosclerosis appears to play a critical role, and oxidative stress and inflammation are important factors in progression (for review, see Textor, 2004).…”

Section: Potential Mechanisms Underlying the Persistent Bace1 Increasementioning

confidence: 88%

“…Indeed, BACE1 levels increase after noxious stimuli, including oxidative stress (Tamagno et al, 2002(Tamagno et al, , 2003Tong et al, 2005), TBI (Blasko et al, 2004), ischemia (Wen et al, 2004), and AD (Fukumoto et al, 2002;Holsinger et al, 2002;Tyler et al, 2002;Yang et al, 2003;. Now, we add energy inhibition to the growing list of stressors that induce BACE1.…”

Section: Physiological Role Of Bace1 Elevationmentioning

confidence: 99%

Energy Inhibition Elevates β-Secretase Levels and Activity and Is Potentially Amyloidogenic in APP Transgenic Mice: Possible Early Events in Alzheimer's Disease Pathogenesis

Velliquette¹,

O’Connor²,

Vassar³

2005

J. Neurosci.

236

186

View full text Add to dashboard Cite

␤-Secretase [␤-site amyloid precursor protein-cleaving enzyme 1 (BACE1)] is the key rate-limiting enzyme for the production of the ␤-amyloid (A␤) peptide involved in the pathogenesis of Alzheimer's disease (AD). BACE1 levels and activity are increased in AD brain and are likely to drive A␤ overproduction, but the cause of BACE1 elevation in AD is unknown. Interestingly, cerebral glucose metabolism and blood flow are both reduced in preclinical AD, suggesting that impaired energy production may be an early pathologic event in AD. To determine whether reduced energy metabolism would cause BACE1 elevation, we used pharmacological agents (insulin, 2-deoxyglucose, 3-nitropropionic acid, and kainic acid) to induce acute energy inhibition in C57/B6 wild-type and amyloid precursor protein (APP) transgenic (Tg2576) mice. Four hours after treatment, we observed that reduced energy production caused a ϳ150% increase of cerebral BACE1 levels compared with control. Although this was a modest increase, the effect was long-lasting, because levels of the BACE1 enzyme remained elevated for at least 7 d after a single dose of energy inhibitor. In Tg2576 mice, levels of the BACE1-cleaved APP ectodomain APPs␤ were also elevated and paralleled the BACE1 increase in both relative amount and duration. Importantly, cerebral A␤40 levels in Tg2576 were increased to ϳ200% of control at 7 d after injection, demonstrating that energy inhibition was potentially amyloidogenic. These results support the hypothesis that impaired energy production in the brain may drive AD pathogenesis by elevating BACE1 levels and activity, which, in turn, lead to A␤ overproduction. This process may represent one of the earliest pathogenic events in AD.

show abstract

“…8,9) Moreover, it has been reported that Ab induces neurotoxicity via oxidative stress, and some antioxidants, such as vitamin E and ferulic acid, protect neurons from Ab-induced apoptosis. 4,10,11) Therefore, the attenuation of oxidative stress through antioxidant therapies may be useful in the treatment/prevention of AD. …”

mentioning

confidence: 99%

Sesaminol Glucosides Protect .BETA.-Amyloid Peptide-Induced Cognitive Deficits in Mice

Ahn

Kim

et al. 2009

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by progressive cognitive function deficits due to the presence of numerous senile plaques and neurofibrillary tangles in certain brain regions.1) The main component of senile plaques is b-amyloid peptide (Ab), which is derived from a large amyloid precursor protein (APP).2) Ab 25-35 contains the residues important for aggregation and toxicity including methionine 35.3) This amyloid fragment has been shown to induce neurotoxicity in vitro as well as in vivo. 4,5) In addition, the intracerebroventricular (i.c.v.) administration of Ab 25-35 into rodent brain induced histological change and cognitive deficit.6,7) The deposition of Ab may cause neuronal death via a number of possible mechanisms including oxidative stress and inflammatory response, which has been suggested to play a key role in AD pathogenesis. 2)Oxidative stress has been hypothesized to play a pivotal role in excitotoxicity, inflammation, and apoptosis in the AD brain. Marker of oxidative stress such as lipid peroxides, protein carbonyl groups, and 8-hydroxyl-2Ј-deoxyguanosine (8-OHdG) are increased in the brains of AD patients than in aged-matched control brains. 8,9) Moreover, it has been reported that Ab induces neurotoxicity via oxidative stress, and some antioxidants, such as vitamin E and ferulic acid, protect neurons from Ab-induced apoptosis. 4,10,11) Therefore, the attenuation of oxidative stress through antioxidant therapies may be useful in the treatment/prevention of AD. 12)Sesame (Sesamum indicum LINN.) is widely known as a natural healthy food, and contains sesame lignan and lignan glycosides.13) Sesame lignan compounds, including sesamin gludosides (SG), have been shown to inhibit endogenous lipid peroxidation as well as oxidative DNA damage in rat liver and kidney.14) These compounds also scavenge peroxyradicals in in vitro experimental systems. [15][16][17] Kang et al. 18) have reported that defatted sesame flour containing SG inhibits lipid peroxidation in hypercholesterolemic rabbits. We also observed that SG had a protective effect against Ab induced neuronal cell death 19) and showed an inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory response in astrocytes. 20) Taking those facts into account, we hypothesized that SG exerts a neuroprotective effect in AD.Since the effect of SG on cognitive function has not been reported, we investigated whether SG can exhibit the protective effect on the Ab 25-35 -induced cognitive impairments. MATERIALS AND METHODSSample Preparation SG isolated form sesame seed was prepared according to the method described by Katsuzaki et al.13) Deffated sesame flour was extracted with distilled water at 95°C for 1 h to obtain a crude extract containing sesaminol glucosides. Crude SG was further purified by Diaion HP 20 (Mitsubishi Chemicals, Co., Tokyo, Japan) column using 60% ethanol. The extracts were concentrated under reduced pressure and freeze-dried for storage until use. Total SG content of the extract was determined by UV spectroscopy, and th...

show abstract

Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons exposed to oxidative stress

Cited by 46 publications

References 56 publications

Amyloid-β Production: Major Link Between Oxidative Stress and BACE1

Amyloid-β Production: Major Link Between Oxidative Stress and BACE1

Energy Inhibition Elevates β-Secretase Levels and Activity and Is Potentially Amyloidogenic in APP Transgenic Mice: Possible Early Events in Alzheimer's Disease Pathogenesis

Sesaminol Glucosides Protect .BETA.-Amyloid Peptide-Induced Cognitive Deficits in Mice

Contact Info

Product

Resources

About