Abstract:
:Alzheimer's disease (AD) is the most common form of dementia in the elderly. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit, but unfortunately, it has been only successful in terms of developing symptomatic treatments. Aβ deposition and neurofibrillary tangles along with neuron and synapse loss are associated with neurotransmitter dysfunction and have been recognized as hallmarks of AD. Furthermore, clinical and preclinical studies point to this neurotransmitter dysfunction as a main factor underlying both cognitive and neuropsychiatric symptoms of the illness. Cholinergic deficit in AD prompted the use of cholinesterase inhibitors as the symptomatic treatment of cognitive decline in AD, however this therapeutic approach provides only modest benefit in the majority of patients. Hence, nowadays research is focused on investigating compounds that could restore cognition and memory in AD patients. GABA is the primary inhibitory neurotransmitter in the central nervous system and GABAergic neurons provide extensive innervation to cholinergic and glutamatergic neurons. It has been shown that dysfunction of the GABAergic system may contribute to cognitive impairment in humans. Significant reductions in GABA levels have been described in severe cases of AD, which could be underlying the behavioral and psychological symptoms of AD. This review examines the involvement of the GABAergic system in both cognitive and non-cognitive behavioural symptoms in AD, providing some pointers for rational drug development.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Solas M,Puerta E,Ramirez MJdoi
10.2174/1381612821666150914121149subject
Has Abstractpub_date
2015-01-01 00:00:00pages
4960-71issue
34eissn
1381-6128issn
1873-4286pii
CPD-EPUB-70339journal_volume
21pub_type
杂志文章,评审abstract::Genetic variation in the receptors and other intracellular targets that mediate the pharmacodynamic effects of drugs can affect therapeutic outcomes. However, at present greater knowledge is available concerning the extent of gene variation in drug metabolizing enzymes that determine drug pharmacokinetics and, in turn...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790112674
更新日期:2010-01-01 00:00:00
abstract::Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393233
更新日期:2002-01-01 00:00:00
abstract::Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by et...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201106092423
更新日期:2020-01-01 00:00:00
abstract::Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395394
更新日期:2002-01-01 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::Lou Gehrig's disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent mode...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170622105513
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Cancer is the world's second-largest cause of death, with an estimated 9.6 million fatalities in 2018. Malignant tumour (cancer) is caused by a mixture of genetic modifications due to the environmental variables that tend to activate or inactivate different genes, ultimately resulting in neoplastic transform...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200701151403
更新日期:2020-01-01 00:00:00
abstract::Cancer disease is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and around 8 million cancer-related deaths yearly. Estimates expect to increase these figures over the next few years. Therefore, it is very important to develop more effective and targeted therapi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150820100812
更新日期:2015-01-01 00:00:00
abstract::Gene therapy, currently, represents one of the new therapies that have emerged for the treatment of different diseases. Between the different approaches that can be chosen concerning this therapy, gene delivery with non-viral systems has focused the attention during the past decades, because of the reduced toxicity co...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901100037
更新日期:2015-01-01 00:00:00
abstract::Gene delivery, a process of introducing foreign functional nucleic acids into target cells, has proven to be a very promising tool for inducing specific gene expression in host cells. Many different technologies have been developed for efficient gene delivery. Among them, electroporation has been adopted in gene deliv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151027152121
更新日期:2015-01-01 00:00:00
abstract::Active pharmaceutical ingredients (APIs) can exist in different polymorphic forms as well as in amorphous state. Polymorphic and amorphous forms of APIs can differ in physicochemical properties which in turn can significantly influence their therapeutic safety and effectiveness of the treatment. This review focuses on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160804100036
更新日期:2016-01-01 00:00:00
abstract::During the last decade immunomodulatory treatments have been shown to influence the natural course of multiple sclerosis (MS). However, demyelination in the central nervous system (CNS) still occurs and repair mechanisms are incomplete leading to neurological deficits. Currently, there is no therapy available to promo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206775193118
更新日期:2006-01-01 00:00:00
abstract::Agitation is commonly seen in acute schizophrenic patients and core symptoms include a wide range of symptom. It requires rapid and effective treatment approaches in order to protect patient and caregiver from potential injury. Clinician's decision of pharmacological treatment should be individualized to the needs and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367472
更新日期:2005-01-01 00:00:00
abstract::Management of hypertension has evolved steadily through 25 years of major clinical trials results modifying both the definition of hypertension and clinical management strategies. Trials experience in heart failure is much less extensive given the far smaller therapeutic market and traditionally often followed on the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454504
更新日期:2003-01-01 00:00:00
abstract::Opioid peptides showing selectivity for delta receptor have been isolated from enzymatic digests of plant proteins. Five peptides were derived from wheat gluten, and named gluten exorphins A5, A4, B5, B4 and C. Two opioid peptides were also released from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco), a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454838
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Endothelial dysfunction is commonly present in estrogen-deficient states, e.g., after menopause. In the search for alternatives to hormone replacement therapy (HRT), treatments based on phytoestrogens or in non-hormonal mechanisms have been under evaluation. OBJECTIVE:Here we aim to present an overview of i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200331084338
更新日期:2020-01-01 00:00:00
abstract::Integrins alpha(1)beta(1) and alpha(2)beta(1) are highly expressed on the microvascular endothelial cells, and blocking of their adhesive properties significantly reduced the VEGF-driven neovascularization ratio and tumor growth in animal models. Hence, inhibitors of the alpha(1)beta(1) and alpha(2) beta(1) integrins,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782023766
更新日期:2007-01-01 00:00:00
abstract::Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty ar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180123101313
更新日期:2018-01-01 00:00:00
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...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798357773
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Enhancing a compound's biological activity is the central task for lead optimization in small molecules drug discovery. However, it is laborious to perform many iterative rounds of compound synthesis and bioactivity tests. To address the issue, it is highly demanding to develop high quality in silico bioacti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200427111309
更新日期:2020-01-01 00:00:00
abstract::Metabolic syndrome (MetS) is a cluster of risk factors, each one individually associated with increased cardiovascular disease risk. Treatment of all components of MetS is expected to result in reduced risk. Treatment of MetS mainly includes lifestyle changes. In addition, drug therapy may be considered, especially co...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789105054
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:From the evidence of failed injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. OBJECTIVE:We seek to stimulate discussions and more research about the possibility of using the already available grow...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201019104201
更新日期:2020-10-18 00:00:00
abstract::Quinone based bioreductive drugs have, potentially, a very versatile use in cancer chemotherapy. They can be activated by DT-diaphorase and hence can be used to target tumour types rich in this (O2)-independent reductase enzyme. Small molecular modifications can substantially reduce specificity for DT-diaphorase and u...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394548
更新日期:2002-01-01 00:00:00
abstract::Hypertension is the most common medical disorder during pregnancy. Approximately 70 percent of women diagnosed with hypertension during pregnancy will have gestational hypertension-preeclampsia. The term gestational hypertension-preeclampsia is used to describe a wide spectrum of patients who may have only mild elevat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381864
更新日期:2005-01-01 00:00:00
abstract::Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Sinc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990465
更新日期:2014-01-01 00:00:00
abstract::Systemic hypersensitivity (HS) to corticosteroids (CS) is paradoxical but does exist. Some patients with a previous contact allergy to topical CS may develop a systemic contact dermatitis (SCD) while receiving CS orally or intravenously. However, a previous contact sensitization is not mandatory for developing a syste...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161013092339
更新日期:2016-01-01 00:00:00
abstract::Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which catalyze CO(2) hydration to bicarbonate and protons. Five genetically distinct classes are known, which represent an excellent example of convergent evolution. Inhibition of α-CAs from vertebrates, including humans, with sulfonamides was exploited clinical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793429797
更新日期:2010-01-01 00:00:00
abstract::Although the obesity epidemic is constantly expanding at very high costs for health care systems, the currently available options for the pharmacotherapy of obesity are very limited. This is not due to lack of interest or research on the subject but rather to the poor efficacy and/or safety profile of the majority of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990302
更新日期:2013-01-01 00:00:00
abstract::Recent advances in DNA sequencing has made it possible to accurately decipher the entire genetic complement of a probiotic bacterium. Increases in sequencing capabilities have been enhanced through improved computer software that can annotate, or identify, the majority of genes encoded by the sequence. The availabilit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612053382377
更新日期:2005-01-01 00:00:00
abstract::Over the last decade, much was learned about the biology of several types of stem and progenitor cells. It has become apparent that various cell sources may have the capacity to promote cardiomyogenesis and new blood vessel formation through different mechanisms, forming the rationale for cell-based therapy in patient...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797904172
更新日期:2011-10-01 00:00:00