Interaction of amyloid binding alcohol dehydrogenase/Aβ mediates up-regulation of peroxiredoxin II in the brains of Alzheimer’s disease patients and a transgenic Alzheimer’s disease mouse model

Yao, Jun; Taylor, Margaret; Davey, Fleur; Ren, Yimin; Aiton, James F.; Coote, Peter J.; Fang, Fang; Chen, John Xi; Yan, Shi Du; Gunn-Moore, Frank J.

doi:10.1016/j.mcn.2007.03.013

Cited by 78 publications

(88 citation statements)

References 23 publications

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“…IP3 and ryanodine receptors) on ER membranes [55]. Notably, ECSIT associates with peroxiredoxin-2 (PRDX2), which becomes oxidatively inactivated when ROS levels exceed the detoxifying abilities of the antioxidant systems, as appears to be the case in mouse AD brains [56]. Conversely, expression of interferonbeta-induced proteins like interferoninduced protein with tetratricopeptide repeats 5 (IFIT5) is up-regulated in AD brain tissues.…”

Section: Role Of Ecsit As a Central Node In The Ad-protein Interactiomentioning

confidence: 99%

Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction

et al. 2012

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Here we postulate that the adapter protein evolutionarily conserved signalling intermediate in Toll pathway (ECSIT) might act as a molecular sensor in the pathogenesis of Alzheimer's disease (AD). Based on the analysis of our AD‐associated protein interaction network, ECSIT emerges as an integrating signalling hub that ascertains cell homeostasis by the specific activation of protective molecular mechanisms in response to signals of amyloid‐beta or oxidative damage. This converges into a complex cascade of patho‐physiological processes. A failure to repair would generate severe mitochondrial damage and ultimately activate pro‐apoptotic mechanisms, promoting synaptic dysfunction and neuronal death. Further support for our hypothesis is provided by increasing evidence of mitochondrial dysfunction in the disease etiology. Our model integrates seemingly controversial hypotheses for familial and sporadic forms of AD and envisions ECSIT as a biomarker to guide future therapies to halt or prevent AD.Editor's suggested further reading in BioEssays Binding of amyloid peptides to domain‐swapped dimers of other amyloid‐forming protein may prevent their neurotoxicity AbstractPlease, also watch the Video Abstract

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Section: Role Of Ecsit As a Central Node In The Ad-protein Interactiomentioning

confidence: 99%

Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction

et al. 2012

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“…Lustbader et al, demonstrated that Aβ binds to the mitochondrial β-amyloid-binding alcohol dehydrogenase (ABAD) (Lustbader et al, 2004), an up-regulated enzyme in patients' brain, which resulted in free radical production and oxidative stress, and increased expression of the cytosolic antioxidant enzyme peroxiredoxin II as a cellular defense response (Yao et al, 2007;Ahsan et al, 2009). In fact, the inhibition of the Aβ-ABAD interaction has been shown to reduce Aβ accumulation and to improve mitochondrial function in transgenic mice and neuroblastoma cells (Lim et al, 2011;Yao et al, 2011).…”

Section: In Alzheimer´s Diseasementioning

confidence: 99%

“…Despite of these evidences, it remains unclear whether the mitochondrial dysfunction responsible of increased ROS production in AD could be a previous step to the Aβ plaques accumulation. In this regard, some studies describe ROS production as an early event before the plaques appearance that could induce the Aβ accumulation (Caspersen et al, 2005;Manczak et al, 2006;Yao et al, 2007;Karuppagounder et al, 2009). …”

Section: In Alzheimer´s Diseasementioning

confidence: 99%

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Morán

Moreno-Lastres

Marín-Buera

et al. 2012

Free Radical Biology and Medicine

139

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For decades mitochondria have been considered static round shaped organelles in charge of energy production. On the contrary, they are highly dynamic cellular components that undergo continuous cycles of fusion and fission influenced, for instance, by oxidative stress, cellular energy requirements, or the cell cycle state. New important functions beyond energy production have been attributed to mitochondria, such as the regulation of cell survival due to their role in the modulation of apoptosis, autophagy and aging. Primary mitochondrial diseases due to mutations in genes involved in these new mitochondrial functions, and the implication of mitochondrial dysfunction in multifactorial human pathologies like cancer, Alzheimer's and Parkinson's diseases, or diabetes has been demonstrated. Therefore, mitochondria are set at a central point of the equilibrium between health and disease, and a better understanding of mitochondrial functions will open new fields to explore the role of these mitochondrial pathways in human pathologies. The present review will dissect the relationships between the activity and assembly defects of the mitochondrial respiratory chain, oxidative damage, and alterations in mitochondrial dynamics, with special focus at their implications in neurodegeneration.

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“…AD is one of the most common neurodegenerative diseases of humans. Amyloid-beta (Abeta) deposits have been found in the brains of patients with AD (Yao et al 2007). The "amyloid cascade hypothesis," one of the well-accepted hypotheses of AD suggests that Aβ and its aggregated forms (including oligomers, protofibrils, and fibrils) may result in toxicity thereby leading to neurodegeneration (Milojevic and Melacini 2011;Shankar et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage

Lai

2014

J Food Sci Technol

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Amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD). Moreover, it has been reported that oxidative stress is involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Recently, docosahexaenoic acid (DHA; C22:6) and eicosapentaenoic acid (EPA; C20:5n-3) have been reported to protect against AD. However, these omega-3 fatty acids are frequently obtained from fish oil and may contain heavy metals. In this study, we utilized Nannochloropsis oceanica to produce omega-3 fatty acid. We observed that when urea levels (nitrogen source) were lowered from 2 to 0.2 g/L in Nannochloropsis oceanica cultures, EPA production increased. Moreover, EPA in Nannochloropsis oceanica effectively promoted antioxidant activity to counter the Abetainduced oxidative stress in Neuro-2A cells. These results indicate that Nannochloropsis oceanica may be potentially used as a therapeutic agent or as a functional food that promotes protection against AD.

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Interaction of amyloid binding alcohol dehydrogenase/Aβ mediates up-regulation of peroxiredoxin II in the brains of Alzheimer’s disease patients and a transgenic Alzheimer’s disease mouse model

Cited by 78 publications

References 23 publications

Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction

Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage

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