Abstract:
:The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect), amyloid-imaging tracers could facilitate the evaluation of the efficacy of anti-amyloid therapies currently under intense development by many major pharmaceutical companies throughout the world. Amyloid-imaging agents could also serve as surrogate markers in early diagnosis and neuropathogenesis studies of Alzheimer's disease and other aging-related neurodegenerative disorders. In this review article, the design and biological evaluation of amyloid-imaging agents are discussed. The structures of these agents vary from large proteins and peptides such as radiolabeled A beta peptides and monoclonal antibodies to small molecules derived from Congo red, Chrysamine-G, thioflavin-T, and Acridine Orange. In vitro studies indicate that amyloid plaques contain multiple binding sites that can accommodate structurally diverse compounds, providing flexibility for radiopharmaceutical design of amyloid imaging agents. Compared to large biomolecules, small molecule radiotracers are often readily accessible through chemical synthesis and can display superior brain permeability. Several small molecule amyloid-imaging radioligands display high binding affinities to A beta and sufficient brain penetration for imaging studies. Recent studies demonstrate the feasibility of imaging amyloid plaques in vivo in human subjects with PET. Imaging NFTs, separately or in concert with A beta plaques, is not as far advanced as imaging A beta plaques and remains to be fully characterized and demonstrated.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Mathis CA,Wang Y,Klunk WEdoi
10.2174/1381612043384772subject
Has Abstractpub_date
2004-01-01 00:00:00pages
1469-92issue
13eissn
1381-6128issn
1873-4286journal_volume
10pub_type
杂志文章,评审abstract::Packaging small-molecule drugs into nanoparticles improves their bio-availability, bio-compatibility and safety profiles. Multifunctional particles carrying large drug payloads for targeted transport, immune evasion and favourable drug release kinetics at the target site, require a certain minimum size usually 30-300 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787002870
更新日期:2009-01-01 00:00:00
abstract::Pituitary adenylyl cyclase activating polypeptide (PACAP) is a neuropeptide with great neuroprotective effects and remarkable therapeutic potential. PACAP activates several cellular pathways to exert its protective effects. Emerging evidence shows that PACAP can modify the levels and activity of cell cycle components ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181127102311
更新日期:2018-01-01 00:00:00
abstract::Drug development for neurodegenerative diseases such as Alzheimer's disease (AD) is a challenge, not only due to the cellular molecular mechanisms involved, but also because of the inherent difficulty of most molecules to cross the blood-brain-barrier (BBB). A promising approach to overcome these drawbacks is developi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150130120358
更新日期:2015-01-01 00:00:00
abstract::Biochemical biomarkers are important candidates for the diagnosis and prognosis of neurological diseases of autoimmune etiology, since they may reflect the presence, nature and intensity of certain immune responses caused by both genetic and environmental processes. Different body fluids such as cerebrospinal fluid (C...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802502143
更新日期:2012-01-01 00:00:00
abstract::Lysine 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 meta...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990487
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Compounds and extracts derived from natural sources continue to stand in the spotlight of drug design owing to their versatile interaction with enzymes, receptors and metabolic pathways. Nanomedicine offers an operative tool for the efficient delivery of natural products, in terms of increased bioavailabilit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170220155540
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND/OBJECTIVE:KRAS-mutant colorectal cancers (CRC) are tumors that are associated with poor prognosis. However, no effective treatments are available to target them. Therefore, we designed and synthesized novel chalcone analogs, small organic molecules, to investigate their effects on KRAS-mutant CRC cells. MET...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200206095400
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Atherosclerosis is a chronic inflammatory disease and a leading cause of coronary artery disease, peripheral vascular disease and stroke. Lipid-laden macrophages are derived from circulating monocytes and form fatty streaks as the first step of atherogenesis. METHODS:An electronic search in major databases ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190830153056
更新日期:2019-01-01 00:00:00
abstract::Stimulation of β-adrenergic receptors in the heart is the most effective endogenous way to increase the mechanical performance of cardiac tissues to meet the requirements of a fight-or-flight situation or stress. On the other hand, sustained activation of cardiac β-receptors initiates maladaptive remodeling of the myo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141029111240
更新日期:2015-01-01 00:00:00
abstract::Mediation of antinociception via opioid receptors located in the periphery is a viable strategy to produce analgesia without the occurrence of side effects associated with stimulation of opioid receptors located in the central nervous system. Peripheral opioid receptors are particularly important in inflammatory pain ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043453036
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. METHODS:This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. RESULTS:In FXS, synaptic dysfunction alte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191102165206
更新日期:2019-01-01 00:00:00
abstract::Inflammation is part of an important mechanism triggered by the innate immune response that rapidly responds to invading microorganisms and tissue injury. One important elicitor of the inflammatory response is the Gram-negative bacteria component lipopolysaccharide (LPS), which induces the activation of innate immune ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990036
更新日期:2014-01-01 00:00:00
abstract::Superparamagnetic iron oxide nanoparticles (SPIONs) comprise a fundamental technology class within the emerging field of nanomedicine, and have been extensively researched for cancer imaging and therapy. This review article will discuss the chemistry and design considerations associated with the synthesis of SPIONs an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660743
更新日期:2014-01-01 00:00:00
abstract::The last quarter of a century has witnessed remarkable progress in the understanding of phosphoinositide 3-kinases (PI3K) signalling and their involvement in different diseases such as cancer, diabetes and inflammation. Nevertheless, many questions remain open and among these the role of genetic and epigenetic regulat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Manufacturing of pharmaceutical solids involves different unit operations and processing steps such as powder blending, fluidization, sieving, powder coating, pneumatic conveying and spray drying. During these operations, particles come in contact with other particles, different metallic, glass or polymer surfaces and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151008124811
更新日期:2015-01-01 00:00:00
abstract::Uveitis is a sight threatening intraocular inflammation accounting for approximately 10% of blindness worldwide. On the basis of aetiology, disease can be classified as infectious or non-infectious; and by anatomical localization of inflammation as anterior, posterior and panuveitis. Non-infectious uveitis is believed...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150316122928
更新日期:2015-01-01 00:00:00
abstract::Schizophrenia is characterised by positive, negative, cognitive, depressive and anxiety symptoms. Over the last decades a number of novel treatment strategies with better clinical efficacy and scope, but with lower side-effect profiles have been developed. These have significantly improved the management and prognosis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150605105215
更新日期:2015-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is marked by cognitive dysfunctions and existence of neuropathological hallmarks such as amyloid plaques, and neurofibrillary tangles. It has been observed that a persistent immune response in the brain has appeared as another neuropathological hall...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200531151004
更新日期:2020-05-31 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
pub_type: 杂志文章,评审
doi:10.2174/138161206777442083
更新日期:2006-01-01 00:00:00
abstract::Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the for...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776361228
更新日期:2006-01-01 00:00:00
abstract::Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170720113216
更新日期:2017-11-16 00:00:00
abstract::Adenosine triphosphate (ATP) synthase produces ATP in cells and is found on the inner membrane of mitochondria or the cell plasma membrane (ectopic ATP synthase). Here, we summarize the functions of ectopic ATP synthase in vascular endothelial cells (ECs). Ectopic ATP synthase is involved in adenosine metabolism on th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794519219
更新日期:2010-01-01 00:00:00
abstract::During the last two decades, the studies on ubiquitination in regulating transcription factor NF-κB activation have elucidated the expanding role of ubiquitination in modulating cellular events by non-proteolytic mechanisms, as well as by proteasomal degradation. The significance of ubiquitination has also been recogn...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319180010
更新日期:2013-01-01 00:00:00
abstract::Hepatitis C virus (HCV) infects an estimated 170 million people globally and persistent infection within the liver is the usual outcome of infection. The resulting liver disease leads to substantial morbidity and to date no vaccine exists. Furthermore the treatments available are frequently ineffective. A minority of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784746806
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Buccal delivery is an alluring course of organization for fundamental medication conveyance and it leads direct access to the systemic flow through the interior jugular vein sidesteps drugs from the hepatic first-pass digestion gives high bioavailability. OBJECTIVE:This article aims at buccal medication con...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200614182013
更新日期:2020-01-01 00:00:00
abstract::Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native prot...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990073
更新日期:2014-01-01 00:00:00
abstract::There is initial evidence, at least in cardiac surgery, that total intra-venous anesthesia (usually a propofol-based total intravenous anesthesia) is associated with an increased mortality when compared to an anesthetic plan including a halogenated anesthetics. The cardiac protective properties of halogenated agents (...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1570161112666140123105536
更新日期:2014-01-01 00:00:00
abstract::This review describes recent advances in the development of DNA-photocleavage agents. Major mechanisms of photosensitized DNA photocleavage are presented and the most popular categories of compounds are considered, which include metal complexes and many organic functional derivatives. DNA-targeted conjugates of photos...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397140
更新日期:2001-11-01 00:00:00
abstract::The nanodelivery of therapeutics into the brain will require a step-change in thinking; overcoming the blood brain barrier is one of the major challenges to any neural therapy. The promise of nanotechnology is that the selective delivery of therapeutics can be delivered through to the brain without causing secondary d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781368648
更新日期:2007-01-01 00:00:00