Abstract:
: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 release of several neurotransmitters, including glutamate, aspartate, GABA, glycine and dopamine, when the release is elicited through cholinergic stimulation but not following depolarization. The effect of beta-amyloid has been observed both in vitro and in vivo in at least three different brain areas (nucleus accumbens, striatum, hippocampus) suggesting that the peptide may exert some general effects even if not all the brain areas have been evaluated. In turn the activation of cholinergic receptors may affect the amyloid precursor protein processing diverting the metabolism toward non-amyloidogenic products. These actions, dissociated from those described in the case of high beta-amyloid concentrations leading to neurotoxic oligomers, may participate to cause dysfunctions in the neurotransmitter activity, in turn leading, at least from a theoretical point of view, to early neuropsychiatric disturbances in the disease. Complexively these observations underscore novel relationships between two main players in Alzheimer's disease pathogenesis that are beta-amyloid and cholinergic transmission. Also emerges the inherent difficulty of targeting beta-amyloid in a context in which the peptide exerts several actions beyond neurotoxicity.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Govoni S,Mura E,Preda S,Racchi M,Lanni C,Grilli M,Zappettini S,Salamone A,Olivero G,Pittaluga A,Marchi Mdoi
10.2174/13816128113199990503subject
Has Abstractpub_date
2014-01-01 00:00:00pages
2525-38issue
15eissn
1381-6128issn
1873-4286pii
CPD-EPUB-54009journal_volume
20pub_type
杂志文章,评审abstract::First generation drug-eluting stents (DES) have significantly improved the treatment options for patients with symptomatic coronary artery disease by decreasing rates of acute vessel closure and restenosis after percutaneous coronary revascularization procedures. However, early enthusiasm was temperd by reports of lat...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::The present mini review offers a brief overview on the preparation and modification of gold nanomaterials (AuNMs) designed for biomedical applications, including biosensors, bioimaging, phototherapy and importantly gene/drug delivery. As biocompatibility is a prerequisite for safe pharmaceutical application, the poten...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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更新日期:2012-01-01 00:00:00
abstract::Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the a...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::Malignant tumors aberrantly overexpress various embryonic genes and proto-oncogenes, including a variety of cancer-testis antigens (CTAs). CTAs belong to a class of testis-derived proteins which are only expressed in germ cells in the male testis, and the expression of CTA genes is entirely silenced in the adult somat...
journal_title:Current pharmaceutical design
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abstract::The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metab...
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journal_title:Current pharmaceutical design
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abstract::Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available ...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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更新日期:2007-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract::During the last years, mass spectrometry has revolutionised protein biochemistry and has advanced to a superior tool for the identification and detailed analysis of peptides and proteins. The high throughput allowed by some mass spectrometry platforms has enabled the important step from analysis of individual proteins...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
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更新日期:2018-02-12 00:00:00
abstract:BACKGROUND:Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies includ...
journal_title:Current pharmaceutical design
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更新日期:2017-01-01 00:00:00
abstract::Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clop...
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abstract::The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of...
journal_title:Current pharmaceutical design
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更新日期:2009-01-01 00:00:00
abstract::Histone lysine methylation can be modified by various writers and erasers. Different from other epigenetic modifications, mono-, di, and tri- methylation distinctly modulate chromatin structure and thereby contribute to the regulation of DNA-based nuclear processes such as transcription, replication and repair on thei...
journal_title:Current pharmaceutical design
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更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:The objective of this study was to apply Quality by Design (QbD) principles on process parameter optimization for the development of hybrid delivery system (combination of (SLNs) and In-situ gelling system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherw...
journal_title:Current pharmaceutical design
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更新日期:2018-01-01 00:00:00
abstract::The concept that the gut microbiota plays a major role in the development of pouchitis in ulcerative colitis patients after restorative proctocolectomy with ileal pouch-anal anastomosis, is widely accepted and supported by a widespread use of some antibiotics (metronidazole and/or ciprofloxacin, rifaximin) to treat th...
journal_title:Current pharmaceutical design
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更新日期:2014-01-01 00:00:00
abstract::Cancer therapies through ionizing radiation or chemotherapeutic treatment may result in DNA double strand breaks (DSBs) in cell. DNA-PK has emerged as an attractive target for drug discovery efforts toward DSBs repair and in V(D)J recombination. Hence, the search for potent and selective DNA-PK inhibitors has received...
journal_title:Current pharmaceutical design
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更新日期:2009-01-01 00:00:00
abstract::Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atheros...
journal_title:Current pharmaceutical design
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更新日期:2014-01-01 00:00:00
abstract::The skin remains an attractive area for drug delivery. The skin, however, often limits the ingress of drugs, because of its very low permeability. Much research, focusing on employing a variety of physical and chemical methods, aimed at reversibly altering skin permeability in favour of compounds, has been reported. O...
journal_title:Current pharmaceutical design
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更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:On a tide of big data, machine learning is coming to its day. Referring to huge amounts of epigenetic data coming from biological experiments and clinic, machine learning can help in detecting epigenetic features in genome, finding correlations between phenotypes and modifications in histone or genes, accele...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2018-01-01 00:00:00