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- Volume 20, Issue 15, 2014
Current Pharmaceutical Design - Volume 20, Issue 15, 2014
Volume 20, Issue 15, 2014
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Getting Rid of Intracellular Aβ - Loss of Cellular Degradation Leads to Transfer Between Connected Neurons
Authors: Lotta Agholme and Martin HallbeckThe sporadic, late onset form of Alzheimer's disease (AD) shares pathological hallmarks with the familial form; however, no clear reason for increased β-amyloid (Aβ) generation has been found in the former. It has long been speculated that the late onset form of AD is caused by reduced degradation and/or clearance of Aβ. Indeed, both intracellular degradation systems, the proteasomal and lysosomal systems, have been Read More
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Disrupting Self-Assembly and Toxicity of Amyloidogenic Protein Oligomers by “ Molecular Tweezers” - from the Test Tube to Animal Models
Authors: Aida Attar and Gal BitanDespite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful diseasemodifying drugs for amyloidoses stems from the nature of the targets for such drugs – primarily oligomers of amyloidogenic proteins, which are distinct fro Read More
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Characterization of the Effect of a Novel γ-secretase Modulator on Aβ: A Clinically Translatable Model
Authors: Erik Portelius, Paulina Appelkvist, Kia Stromberg and Kina HoglundAlzheimer's disease (AD) is a slowly progressing disease and the evaluation of clinical effects of candidate drugs requires large clinical cohorts as well as long treatment trials. There is a great need for central biomarkers and translatable pre-clinical models to provide early indication of treatment effects. We set out to evaluate the guinea pig as a clinically translatable model looking at Aβ peptides. Our data demonstrate Read More
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In Vivo Application of beta Amyloid Oligomers: A Simple Tool to Evaluate Mechanisms of Action and New Therapeutic Approaches
Authors: Claudia Balducci and Gianluigi ForloniAlzheimer's disease (AD) is a neurodegenerative disorder characterized by cerebral accumulation of extracellular amyloid β (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau protein, two main lesions which appear sequentially during the disease progression. In the last decade numerous studies have proposed small soluble aggregates of Aβ, known as oligomers, as the species responsible for synaptic dysfunctio Read More
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The Effects of Soluble Aβ Oligomers on Neurodegeneration in Alzheimer's Disease
More LessThe neurodegenerative process that defines Alzheimer’s disease (AD) is initially characterized by synaptic alterations followed by synapse loss and ultimately cell death. Decreased synaptic density that precedes neuronal death is the strongest pathological correlate of cognitive deficits observed in AD. Substantial synapse and neuron loss occur early in disease progression in the entorhinal cortex (EC) and the CA1 region of the hip Read More
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Disruption of Zinc Neuromodulation by Aß Oligomers : Therapeutic Implications
Authors: Emily C. Vogler and Jorge BusciglioSo far, therapeutics focusing on reducing levels of amyloid beta for treatment of Alzheimer’s disease have not been successful in completing clinical trials to come to market, suggesting the need of a wider perspective and the consideration of novel targets of intervention to slow or halt the progression of this disease. One such target is soluble amyloid beta in oligomeric forms, which have been demonstrated to bind with Read More
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Dangerous Liaisons between Beta-Amyloid and Cholinergic Neurotransmission
The review examines the multifaceted interactions between cholinergic transmission and beta-amyloid suggesting a continuum in the action of the peptide that at low concentrations (picomolar-low nanomolar) may directly stimulate nicotinic cholinergic receptor while desensitizing them at increasing concentrations (high nanomolar-low micromolar). In addition high beta-amyloid concentrations may reduce the synaptic rele Read More
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Modulatory Activity of Soluble Beta Amyloid on HPA Axis Function in Rats
Despite the consolidation of the amyloid hypothesis, the main component of senile plaques in Alzheimer’s disease (AD), recent findings have led to a conceptual shift opening new questions about the potential physiological role of this peptide. In addition, soluble beta amyloid (sBA), in transgenic AD model, resulted to be increased after chronic and acute stress and alterations in cortisol levels have been reported in AD. Impaired h Read More
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Soluble Amyloid-β Levels and Late-Life Depression
Authors: Ricardo S. Osorio, Tyler Gumb and Nunzio PomaraLate-Life Major Depression (LLMD) is a complex heterogeneous disorder that has multiple pathophysiological mechanisms such as medical comorbidity, vascular-related factors and Alzheimer’s disease (AD). There is an association between LLMD and AD, with LLMD possibly being a risk factor for, or early symptom of AD and vascular dementia. Whether depression is an etiologic risk factor for dementia, or part of the de Read More
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Glutamine, Glucose and other Fuels for Cancer
Tumor cells suffer a metabolic reprogramming which allows them to use metabolic fuels (glucose, glutamine, lipids) through anabolic fates to support their enhanced proliferation and other carcinogenesis-related features. The present review tries to address and summarize the broad and growing information available about this reprogramming, whose pieces, put together, make up a complex scheme that encompasses dif Read More
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Reprogrammed Metabolism of Cancer Cells as a Potential Therapeutic Target
Authors: Jaap Keijer and Dorien A.M. van DartelMetabolism in cancer cells is reprogrammed. Cancer cells largely depend on glycolysis for ATP production. The metabolic alterations in cancer cells facilitate resistance to cell death as well as biosynthesis of nucleotides and lipids, building blocks for growth. The reprogrammed metabolism is increasingly seen as a target in cancer therapy. This review describes the metabolic reprogramming of cancer cells and illustrates how t Read More
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Pyruvate Kinase M2: Regulatory Circuits and Potential for Therapeutic Intervention
Authors: Vibhor Gupta, Kathryn E. Wellen, Sybille Mazurek and Rameshwar N. K. BamezaiCancer cells are characterized by reprogramming of energy metabolism. Over the last decade, understanding of the metabolic changes that occur in cancer has increased dramatically, with great interest in targeting metabolism for cancer therapy. Pyruvate kinase isoenzyme type M2 (abbreviations: PKM2, M2-PK) plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isofor Read More
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AMPK as a Potential Anticancer Target - Friend or Foe?
Authors: Hsiao-Ching Chuang, Chih-Chien Chou, Samuel K. Kulp and Ching-Shih ChenAdenosine monophosphate-activated protein kinase (AMPK) is a key player in maintaining energy homeostasis in response to metabolic stress. Beyond diabetes and metabolic syndrome, there is a growing interest in the therapeutic exploitation of the AMPK pathway in cancer treatment in light of its unique ability to regulate cancer cell proliferation through the reprogramming of cell metabolism. Although many studies sup Read More
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Targeting SREBP-1-driven Lipid Metabolism to Treat Cancer
Authors: Deliang Guo, Erica Hlavin Bell, Paul Mischel and Arnab ChakravartiMetabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that controls lipid metabolism, is a critical link between oncogenic signaling and tumor Read More
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Acetylation Control of Cancer Cell Metabolism
Authors: Ruiting Lin, Xin Zhou, Wei Huang, Di Zhao, Lei Lv, Yue Xiong, Kun-Liang Guan and Qun-Ying LeiLysine acetylation plays an essential role in metabolism. Five individual studies have identified that a large number of cellular proteins are potentially acetylated. Notably, almost every enzyme involved in central metabolic pathways such as glycolysis, the TCA cycle, fat acid metabolism, urea cycle and glycogen metabolism, is acetylated in response to nutrition fluctuations. Metabolic reprogramming is a critical hallmark d Read More
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A Dual Role for Sirtuin 1 in Tumorigenesis
Authors: Yujiang Fang and Michael B. NichollSirtuin 1 (SIRT1) is an NAD+-dependent histone deacetylase which regulates many normal physiological and pathological processes. In addition to its place in cellular energy metabolism, increasing evidence shows a role for SIRT1 in tumorigenesis, wherein it can function as either a tumor promoter or suppressor. Its function in malignancy varies with concentration, cellular location, temporal and spatial distribution, and reg Read More
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Targeted Cancer Therapeutics: Biosynthetic and Energetic Pathways Characterized by Metabolomics and the Interplay with Key Cancer Regulatory Factors
Authors: Ngoc-Ha T. Dang, Arvind K. Singla, Emily M. Mackay, Frank R. Jirik and Aalim M. WeljieReprogramming of energy metabolism has recently been added to the list of hallmarks that define cancer. Cellular metabolism plays a central role in cancer initiation and progression to metastatic disease. Genotypic and phenotypic metabolic alterations are seen throughout tumourigenesis, allowing cancer cells to sustain increased rates of proliferation. Furthermore, this shift fuels necessary substrates for nucleotide, protein, Read More
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A Systems Biology Road Map for the Discovery of Drugs Targeting Cancer Cell Metabolism
Despite their different histological and molecular properties, different types of cancers share few essential functional alterations. Some of these cancer hallmarks may easily be studied in in vitro cultures, while others are related to the way in which tumors grow in vivo. According to the systems biology paradigm, complex cellular functions arise as system-level properties from the dynamic interaction of a large number o Read More
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Volumes & issues
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Volume 31 (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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- Issue 1
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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