Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease

Jo, Dong-Gyu; Arumugam, Thiruma V.; Woo, Ha-Na; Park, Jong‐Sung; Tang, Sung‐Chun; Mughal, Mohamed R.; Hyun, Dong Hoon; Park, Jun Hyung; Choi, Yun-Hyung; Gwon, A-Ryeong; Camandola, Simonetta; Cheng, Ann‐Lii; Cai, Huaibin; Song, Weihong; Markesbery, William R.; Mattson, Mark P.

doi:10.1016/j.neurobiolaging.2008.07.003

Cited by 90 publications

(67 citation statements)

References 28 publications

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“…Second, our data revealed the existence of a positive feedback loop in which c-secretase activity results in up-regulation of BACE1 expression. Previously Minopoli et al (2007) had shown a correlation between the induction of OS and the increase of c-secretase cleavage on APP and then Jo et al (2010) confirmed the finding that c-secretase up-regulates BACE1 expression.…”

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

confidence: 73%

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

et al. 2011

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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.

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

confidence: 73%

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

et al. 2011

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“…Inferior parietal lobule and cerebellum specimens from the brains of 5 patients with AD and 5 control subjects that had been enrolled in the University of Kentucky Alzheimer's Disease Center Autopsy Program were used for this study. All patients with AD met both clinical diagnostic criteria and neuropathological diagnostic criteria of AD (41,42). The control subjects had no history or neuropathological signs of a brain disorder.…”

Section: Methodsmentioning

confidence: 99%

Down-regulation of Mortalin Exacerbates Aβ-mediated Mitochondrial Fragmentation and Dysfunction

Park

Shin

Jeong

et al. 2014

Journal of Biological Chemistry

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Background: Mitochondrial dysfunction is associated with neuronal disorders, and mitochondrial dynamics are altered in neurodegenerative diseases. Results: Inhibition of mortalin potentiates amyloid-␤-mediated mitochondrial dysfunction and cytotoxicity. Conclusion: Inhibition of mortalin could lead to mitochondrial dysfunction through mitochondrial fragmentation. Significance: Activation of mortalin may antagonize the progression of A␤-mediated neuronal injury in which mitochondrial dysfunction has a key role.

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“…Oxidative stress-induced BACE1 expression is regulated by γ-secretase activity, providing evidence of a feed-forward pathogenic mechanism of AD in which oxidative stress increases Aβ production, which then enhances oxidative stress (29). Molecular identification of the γ-secretase complex has shown that four different members are essential for this enzymatic activity: presenilin 1 (PS1), anterior pharynx-defective (APH-1), presenilin enhancer 2 (PEN-2), and nicastrin (NCT) (27,28).…”

Section: Figmentioning

confidence: 99%

Effects of chronic alcohol consumption on expression levels of APP and Aβ-producing enzymes

Kim¹,

Jeong²,

Yang³

et al. 2011

BMB Reports

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Chronic alcohol consumption contributes to numerous diseases, including cancers, cardiovascular diseases, and liver cirrhosis. Epidemiological studies have shown that excessive alcohol consumption is a risk factor for dementia. Along this line, Alzheimer's disease (AD) is the most common form of dementia and is caused by the accumulation of amyloid-β (Aβ plaques in neurons. In this study, we hypothesized that chronic ethanol consumption is associated with pathological processing of APP in AD. To investigate the relationship between chronic alcohol consumption and Aβ production, brain samples from rats fed an alcohol liquid diet for 5 weeks were analyzed. We show that the expression levels of APP, BACE1, and immature nicastrin were increased in the cerebellum, hippocampus, and striatum of the alcohol-fed group compared to the control group. Total nicastrin and PS1 levels were induced in the hippocampus of alcohol-fed rats. These data suggest that the altered expression of APP and Aβ-producing enzymes possibly contributes to the chronic alcohol consumption-mediated pathogenesis of AD. [BMB reports 2011; 44(2): 135-139]

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Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease

Cited by 90 publications

References 28 publications

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

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

Down-regulation of Mortalin Exacerbates Aβ-mediated Mitochondrial Fragmentation and Dysfunction

Effects of chronic alcohol consumption on expression levels of APP and Aβ-producing enzymes

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