Amyloid‐Beta Interaction with Mitochondria

Pagani, Lucia; Eckert, Anne

doi:10.4061/2011/925050

Cited by 219 publications

(190 citation statements)

References 156 publications

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“…This is in accordance with the modified model of the amyloid cascade hypothesis that suggests that the toxic Ab species may be soluble intracellular aggregates instead of extracellular insoluble plaques (Fig. 1B) [35]. Nevertheless, what seems certain is the importance of the regulation/ modulation balance in the Ab pool between intracellular and extracellular compartments under patho-physiological conditions (Fig.…”

Section: Mitochondrial Dysfunction: Oxidative Stresssupporting

confidence: 89%

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: Mitochondrial Dysfunction: Oxidative Stresssupporting

confidence: 89%

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

et al. 2012

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“…These changes in expression levels may be responsible for decreased mitochondrial function by causing structural abnormalities in and defective trafficking of mitochondria in HD 97 . In AD, mitochondria, especially synaptic mitochondria, show agedependent Aß accumulation 98,99 , which enhances the permeability of the mitochondrial permeability transition pore and causes the generation of reactive oxygen species 99 . Clinical trials of antioxidants that might ameliorate oxidative stress, DNA and mitochondrial damage, have not yielded conclusive results in patients with either AD or HD 100,101 .…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Ehrnhoefer

Wong

Hayden

2011

Nat Rev Drug Discov

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Neurodegenerative diseases exemplified by Alzheimer's and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a 'model' for Alzheimer's disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways.

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“…This whole process is initiated by APO4 within astrocytes 148 . CypD's involvement in the mPTP complex has also found application in Alzheimer's disease due to recent reports which suggest that Aβ proteins influence mPTP formation when in a complex with CypD 149 . Conversely, the loss of Pin1 expression is correlated with Alzheimer's disease and neurodegeneration due to Pin1's important role in the stabilisation and regulation of tau and Aβ proteins 42 .…”

Section: The Role Of Ppiases In Neurodegenerationmentioning

confidence: 99%

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

McClements¹,

Annett²,

Yakkundi³

et al. 2015

CMP

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Peptidyl prolyl isomerases (PPIases) are proteins belonging to the immunophilin family and are characterised by their cis-trans isomerization activity at the X-Pro peptide bond, in addition to their tetratricopeptide repeat (TPR) domain, important for interaction with the molecular chaperone, Hsp90. Due to this unique structure these proteins are able to facilitate proteinprotein interactions which can impact significantly on a range of cellular processes such as cell signalling, differentiation, cell cycle progression, metabolic activity and apoptosis.Malfunction and/or dysregulation of most members of this class of proteins promotes cellular damage and tissue/organ failure, predisposing to ageing and age-related diseases. Many individual genes within the PPIase family are associated with several age-related diseases including cardiovascular diseases (CVDs), atherosclerosis, type II diabetes (T2D), chronic kidney disease (CDK), neurodegeneration, cancer and age-related macular degeneration (AMD), in addition to the ageing process itself. This review will focus on the different roles of PPIases, and their therapeutic/biomarker potential in these age-related vascular diseases.

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Amyloid‐Beta Interaction with Mitochondria

Cited by 219 publications

References 156 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

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

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