Defining the role of the Bcl-2 family proteins in Huntington’s disease

Sassone, Jenny; Maraschi, AnnaMaria; Sassone, Francesca; Silani, Vincenzo; Ciammola, Andrea

doi:10.1038/cddis.2013.300

Cited by 30 publications

(23 citation statements)

References 91 publications

(123 reference statements)

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“…As mitochondrial dysfunction is a hallmark of Aβ-induced neuronal toxicity in AD [8][9][10], there is no doubt that the Bcl-2-family proteins are involved in the regulation of neuronal apoptotic cell death [36][37][38]. To date, the exact mechanism which the Bcl-2 family proteins act upon the apoptotic pathway is still not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway

Tan

Kim

2016

Molecules

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Abstract:Alzheimer's disease is considered one of the major neurodegenerative diseases and is characterized by the production of β-amyloid (Aβ) proteins and progressive loss of neurons. Biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, was used in the present study as a potential alternative to estrogen replacement therapy via the investigation of its neuroprotective effects against Aβ 25-35 -induced toxicity, as well as of its potential mechanisms of action in PC12 cells. Exposure of these cells to the Aβ 25-35 protein significantly increased cell viability loss and apoptosis. However, the effects induced by Aβ 25-35 were markedly reversed in the present of biochanin A. Pretreatment with biochanin A attenuated the cytotoxic effect of the Aβ 25-35 protein by decreasing viability loss, LDH release, and caspase activity in cells. Moreover, we found that expression of cytochrome c and Puma were reduced, alongside with the restoration of Bcl-2/Bax and Bcl-xL/Bax ratio in the presence of biochanin A, which led to a decrease in the apoptotic rate. These data demonstrate that mitochondria are involved in the protective effect of biochanin A against Aβ [25][26][27][28][29][30][31][32][33][34][35] and that this drug attenuated Aβ 25-35 -induced PC12 cell injury and apoptosis by preventing mitochondrial dysfunction. Thus, biochanin A might raise a possibility as a potential therapeutic agent for Alzheimer's disease and other related neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway

Tan

Kim

2016

Molecules

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“…This commitment culminates in the permeabilization of the outer mitochondrial membrane (OMM). 2 As a result, factors are released from the mitochondria that trigger downstream signaling for apoptosis including the activation of caspases (1,5). Therefore, different steps that lead to the permeabilization of the OMM have been attractive therapeutic targets (6) to either initiate apoptosis in cancerous cells, or inhibit a constitutive activation present in autoimmune or degenerative diseases.…”

mentioning

confidence: 99%

“…A complex network of proteins and signals ensures that cells grow and replicate until a defined time where they are replaced by new cells. Disruption in this mechanism can lead to neurodegenerative, cancerous, or autoimmune diseases, (1)(2)(3). The Bcl-2 family of proteins is primarily responsible for initiating apoptosis through an intrinsic (mitochondria) pathway, where signals directly sensed by the cells can initiate the cascade of events that lead to a commitment to cell death (3,4).…”

mentioning

confidence: 99%

Conformational Rearrangements in the Pro-apoptotic Protein, Bax, as It Inserts into Mitochondria

Gahl

et al. 2014

Journal of Biological Chemistry

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Background:The translocation of pro-apoptotic protein Bax from the cytosol to the mitochondria signals the commitment to cell death. Results: Distances between locations in Bax were measured during translocation in live cells. Conclusion:The conformational changes that coincide with the commitment to apoptosis were identified. Significance: This information is crucial for the development of more effective therapeutics that target apoptosis.

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“…Furthermore, mitochondrion is a key organelle regulating cell death via two ways. On one hand, the lack of ATP which is mainly produced in the mitochondria via Oxidative phosphorylation will lead to cell death through necrosis [10] and on the other hand, a variety of signalling apoptotic processes are linked to mitochondria [11], such as for example the family Bcl-2 which regulates apoptosis through mitochondrial permeability [10] [12]. The Inositol Phosphate…”

Section: Finding Metabolic and Molecular Processes Crosstalk Between mentioning

confidence: 99%

Metabolic and signalling network map integration: application to cross-talk studies and omics data analysis in cancer

Sompairac

Modamio

Barillot

et al. 2018

Preprint

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Background:The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have never been integrated together. We aim at filling in this gap by creating an integrated resource of both signalling and metabolic pathways allowing a visual exploration of multi-level omics data and study of cross-regulatory circuits between these processes in health and in disease. Results:We combined two comprehensive manually curated network maps. Atlas of Cancer Signalling Network (ACSN), containing mechanisms frequently implicated in cancer; and ReconMap 2.0, a comprehensive reconstruction of human metabolic network. We linked ACSN and ReconMap 2.0 maps via common players and represented the two maps as interconnected layers using the NaviCell platform for maps exploration. In addition, proteins catalysing metabolic reactions in ReconMap 2.0 were not previously visually represented on the map canvas. This precluded visualisation of omics data in the context of ReconMap 2.0. We suggested a solution for displaying protein nodes on the ReconMap 2.0 map in the vicinity of the corresponding reaction or process nodes. This permits multi-omics data visualisation in the context of both map layers. Exploration and shuttling between the two map layers is possible using Google Maps-like features of NaviCell. The integrated ACSN-ReconMap 2.0 resource is accessible online and allows data visualisation through various modes such as markers, heat maps, bar-plots, glyphs and map staining. The integrated resource was applied for comparison of immunoreactive and proliferative ovarian cancer subtypes using transcriptomic, copy number and mutation multi-omics data. A certain number of metabolic and signalling processes specifically deregulated in each of the ovarian cancer sub-types were identified.

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Defining the role of the Bcl-2 family proteins in Huntington’s disease

Cited by 30 publications

References 91 publications

Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway

Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway

Conformational Rearrangements in the Pro-apoptotic Protein, Bax, as It Inserts into Mitochondria

Metabolic and signalling network map integration: application to cross-talk studies and omics data analysis in cancer

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