Abstract:
:Amyotrophic lateral sclerosis (ALS) is an age-related neurodegenerative disorder that is believed to have complex genetic and environmental influences in the pathogenesis, but etiologies are unidentified for most patients. Until the major causes are better defined, drug development is directed at downstream pathophysiological mechanisms, themselves incompletely understood. For nearly 30 years, glutamate-induced excitotoxicity has lain at the core of theories behind the spiraling events, including mitochondrial dysfunction, oxidative stress, and protein aggregation, that lead to neurodegenerative cell death. One drug, riluzole, which possesses anti-glutamatergic properties, is approved as neuroprotective for ALS. Following the achievement of the riluzole trials, numerous other agents with similar mechanisms have been tested without success. This article provides an overview of excitotoxicity in ALS, focusing on the events that contribute to excess glutamate, how the excess might damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. The work highlights clinical trials of drugs that have targeted the glutamate system, comments on the potential role of glutamate as a biomarker and concludes with a section on future directions for the field. As research uncovers elusive etiologies and brings clarity to pathophysiological mechanisms, the success of new interventions will increasingly depend on the design of agents that target particular mechanisms for specific individuals. The heady future of personalized drug regimens for ALS rests with medicinal chemists, the scientists whose ideas and work produce these designer drugs.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Blasco H,Mavel S,Corcia P,Gordon PHdoi
10.2174/0929867321666140916120118subject
Has Abstractpub_date
2014-01-01 00:00:00pages
3551-75issue
31eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-62359journal_volume
21pub_type
杂志文章,评审abstract::Endothelial cells (ECs) play a pivotal role in physiological and altered tissue neovascularization. They face multiple morphological, biochemical and functional changes during the different phases of angiogenesis, under the regulation of a great number of proangiogenic and antiangiogenic signals, including soluble and...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709789878210
更新日期:2009-01-01 00:00:00
abstract::Snake venoms are natural sources of biologically active molecules that are able to act selectively and specifically on different cellular targets, modulating physiological functions. Thus, these mixtures, composed mainly of proteins and peptides, provide ample and challenging opportunities and a diversified molecular ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666161028155611
更新日期:2017-01-01 00:00:00
abstract::Andrographolide, the main bioactive component separated from Andrographis paniculata in 1951, have been scrutinized with modern drug discovery approach for anti-inflammatory properties since 1984. Identifying new uses for existing drugs can be facilitated by evidence linking them to known or yet undiscovered drug targ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666200810135604
更新日期:2020-08-10 00:00:00
abstract::Targeted therapy has been recently highlighted due to the reduction of side effects and improvement in overall efficacy and survival to different types of cancers. Considering the approval of many monoclonal antibodies in the last twenty years, cancer treatment can be accomplished by the combination of monoclonal anti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666200525161359
更新日期:2020-05-25 00:00:00
abstract::Voltage-gated sodium channels are large transmembrane protein complexes responsible for the propagation and transmission of electrical impulses through nerve, muscle and endocrine cells and cell systems. Dysregulated expression and/or functional changes of ion channel isoforms are found in many associated pathological...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113206660257
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Steroid hormones belong to a group of low-molecular weight compounds which are responsible for maintenance of various body functions, thus, their accurate assessment is crucial for evaluation of biosynthetic defects. The development of reliable methods allowing disease diagnosis is essential to improve early...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666171113120810
更新日期:2019-01-01 00:00:00
abstract::Atrial fibrillation represents a major clinical, social and economical matter, and its importance is expected to increase even more in the near future. The progressive ageing of population is associated with an inevitable rising in incidence and prevalence of this rhythm disorder, which limits functional capability, f...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706777441940
更新日期:2006-01-01 00:00:00
abstract::Analytical chemists have increasingly turned their attention to drug discovery and drug analysis and to solve fundamental questions of biological significance in physiology and genetics. New technologies have been developed, and a variety of instruments have been redesigned for biomedical applications. The development...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867310504050501
更新日期:2005-01-01 00:00:00
abstract::Potent enzyme inhibitors have long been recognized as powerful tools for assessing the physiological roles of enzymes and have led to the therapeutic drugs able to modulate their activities in vivo. However, to be valuable tools such inhibitors should be selective so that they do not interfere with other members of th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023371120
更新日期:2002-02-01 00:00:00
abstract::The existence of functional NT/dopamine interactions in the central nervous system has been extensively documented. Among others, a possible molecular mechanism underlying the NT-induced modulation of dopamine release is a direct antagonistic NTS(1)/D(2) receptor interaction. More recently, neurochemical experiments a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803414268
更新日期:2012-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180214112536
更新日期:2018-01-01 00:00:00
abstract::Reversible phosphorylation is a key mechanism for regulating the biological activity of many human proteins that affect a diverse array of cellular processes, including protein-protein interactions, gene transcription, cell-cycle progression and apoptosis. Once viewed as simple house keeping enzymes, recent studies ha...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023368836
更新日期:2002-11-01 00:00:00
abstract::Both zinc and copper are essential minerals that are required for various cellular functions. Although these metals are essential, they can be toxic at excess amounts, especially in certain genetic disorders. Zinc and copper homeostasis results from a coordinated regulation by different proteins involved in uptake, ex...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986705774462950
更新日期:2005-01-01 00:00:00
abstract::Kit is a growth factor receptor of the type III tyrosine kinase family, whose gain-of-function mutations have been identified as driving causes of different kinds of tumours. It thus represents a viable drug target, and the development of Kit inhibitors has been shown to be a promising therapeutic concept. This review...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711796150504
更新日期:2011-01-01 00:00:00
abstract::Normal somatic stem cells (SC) are naturally resistant to chemotherapeutic agents due to their expression of various membrane transporter molecules (such as MDR-1), detoxifying enzymes and DNA repair proteins. In addition, they also have a slow rate of cell turnover and therefore escape from chemotherapeutic agents th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788186147
更新日期:2009-01-01 00:00:00
abstract::Osteoporosis is characterized by reduced bone mass and structural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. Bone loss further increases in postmenopausal women when the ovaries stop making estrogens. Women undergoing treatment for osteoporosis require l...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710791959738
更新日期:2010-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666141106122628
更新日期:2015-01-01 00:00:00
abstract::Obesity is a chronic disease characterized by the accumulation of excess adipose tissue associated with an increased risk of multiple morbidities and mortality. At the present time, only three drugs have been approved by the Food and Drug Administration (FDA) for the treatment of obesity. Agonists and antagonists of s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784049621
更新日期:2008-01-01 00:00:00
abstract::A challenging question in biology is how cells control their shape and volume. The relative abundance of organelles can be radically modified to comply with a new task, an example being the massive development of the endoplasmic reticulum (ER) in Ig-secreting plasma cells. The ER is the site where secretory proteins a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707780830952
更新日期:2007-01-01 00:00:00
abstract::Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710793176339
更新日期:2010-01-01 00:00:00
abstract::Two-component signal transduction systems and their expanded variants known as phosphorelays are integral elements of the virulence and antimicrobial resistance responses of a wide range of pathogenic bacteria and fungi and also regulate essential functions. As a consequence, two-component systems and phosphorelays ar...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043455765
更新日期:2004-03-01 00:00:00
abstract::gammadelta T lymphocytes are involved in the defence from viral and mycobacterial infections; however they are also responsible for autoimmune reactions. Herein, we discuss the characteristics of these cells, focusing on the mechanism(s) underlying extravasation and tissue localization. We show that Vdelta1 and Vdelta...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707782793835
更新日期:2007-01-01 00:00:00
abstract::The use of dopaminergic agonists is key in the treatment of Parkinson's disease and related central nervous system (CNS) neurodegenerative disorders. Despite there are a number of commercialized dopaminergic agonists that are currently being used successfully in the first stages of the disease, they often fail to prov...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160504103621
更新日期:2016-01-01 00:00:00
abstract::Small interfering RNA (siRNA) constitutes an excellent way of knocking down genes. However, it requires the use of delivery systems to reach the target cells, especially to neuronal cells. Dendrimers are one of the most widely used synthetic nanocarriers for siRNA delivery. However, due to the complexity of the dendri...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867311209024929
更新日期:2012-01-01 00:00:00
abstract::The neuropeptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems and it is known that after binding to the neurokinin-1 (NK-1) receptors, SP regulates many biological functions in the central nervous system such as emotional behaviour, stress, depression, anxiety, em...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795496746
更新日期:2011-01-01 00:00:00
abstract::Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707782023659
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:We found a novel marine drug, SZ-685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of thi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867311320160007
更新日期:2013-01-01 00:00:00
abstract::It is well accepted that inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is one of high risk factors for colorectal cancer (CRC). This supports the notion that inflammation plays a key role in cancer development. Epidemiologic studies have shown that vitamin D (Vit D) deficiency is ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867323666161202153028
更新日期:2017-01-01 00:00:00
abstract::Among the members of the 5'-nucleotidase family, there is only one membrane-bound ectosolic isoenzyme. This esterase prefers AMP as substrate but can hydrolyze a number of purine and pyrimidine phosphorylated compounds, indicating that no evolutive pressure to develop a more restricted specificity was exerted on this ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320340007
更新日期:2013-01-01 00:00:00
abstract::Neurodegenerative disorders (NDDs) like Alzheimer's disease, Parkinson's disease and Huntington's disease are a heterogeneous group of disorders with the progressive and severe loss of neurons. There are no full proof cures for these diseases, and only medicines are available that can alleviate some of the symptoms. D...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170112101837
更新日期:2018-01-01 00:00:00