Abstract:
:The mechanisms underlying neurodegeneration in amyotrophic lateral sclerosis (ALS) are multifactorial and include genetic and environmental factors. Nowadays, it is well accepted that neuronal loss is driven by non-cell autonomous toxicity. Non-neuronal cells, such as astrocytes, have been described to significantly contribute to motoneuron cell death and disease progression in cell culture experiments and animal models of ALS. Astrocytes are essential for neuronal survival and function by regulating neurotransmitter and ion homeostasis, immune response, blood flow and glucose uptake, antioxidant defence and growth factor release. Based on their significant functions in "housekeeping" the central nervous system (CNS), they are no longer thought to be passive bystanders but rather contributors to ALS pathogenesis. Findings from animal models have broadened our knowledge about different pathomechanisms in ALS, but therapeutic approaches to impede disease progression failed. So far, there is no cure for ALS and effective medication to slow down disease progression is limited. Targeting only a single aspect of this multifactorial disease may exhibit therapeutic limitations. Hence, novel cellular targets must be defined and new pharmaceutical strategies, such as combinatorial drug therapies are urgently needed. The present review discusses the physiological role of astrocytes and current hypotheses of astrocyte pathology in ALS. Furthermore, recent investigation of potential drug candidates in astrocyte cell culture systems and animal models, as well as data obtained from clinical trials, will be addressed. The central role of astrocytes in ALS pathogenesis makes them a promising target for pharmaceutical interventions.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Johann Sdoi
10.2174/1381612823666170615110856subject
Has Abstractpub_date
2017-01-01 00:00:00pages
5022-5036issue
33eissn
1381-6128issn
1873-4286pii
CPD-EPUB-84122journal_volume
23pub_type
杂志文章,评审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
abstract::Lipid markers are well established predictors of vascular disease. The most frequently measured lipid variables are total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. In this review we consider the predictive value of these variables and other more specialis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367409
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:R. Schofield (1978) proposed a hypothesis of hematopoietic stem cells (HSCs) niche (specialized cell microenvironment). An existence of osteoblastic and vascular niches for HSCs has been postulated since 2003. At the same time, the discussion about the existence and functioning of niche for multipotent mesen...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180829154119
更新日期:2018-01-01 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:BACKGROUND:Cancer is a set of diseases formed by abnormal growth of cells leading to the formation of the tumor. The diagnosis can be made through symptoms' evaluation or imaging tests, however, the techniques are limited and the tumor detection may be late. Thus, pharmaceutical nanotechnology has emerged to optimize t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200219094853
更新日期:2020-01-01 00:00:00
abstract::Natural products, or their synthetic derivatives are a treasure trove to find potential candidates for novel drugs for human treatment. The selection of diamonds from the huge pile of worthless stone is a critical--and difficult--stage in the discovery pipeline. Of all the factors to be considered, perhaps the most im...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151002114227
更新日期:2015-01-01 00:00:00
abstract::G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799040493
更新日期:2012-01-01 00:00:00
abstract::Since identifying a transmissible agent responsible for tumorigenesis in chickens, the v-Src oncogene, significant progress has been made in determining the functions of its cellular homologue. c-Src is the product of the SRC gene and has been found both over-expressed and highly activated in a number of human cancers...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507576
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170809115429
更新日期:2017-01-01 00:00:00
abstract::Insight is provided herein into the novel mechanisms of cardiometabolic risk. Previous reports, including the epidemiological work of the Turkish Adult Risk Factor study, indicated that proinflammatory state and oxidative stress are crucial for evaluating cardiometabolic risk. Autoimmune pathways in the course of oxid...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282004140213145551
更新日期:2014-01-01 00:00:00
abstract::Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795703735
更新日期:2011-01-01 00:00:00
abstract::The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797247541
更新日期:2011-01-01 00:00:00
abstract::Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660744
更新日期:2014-01-01 00:00:00
abstract::Cardiovascular disease (CVD) is one of the major lifestyle associated disorders and leading causes of death worldwide. The incidence of CVD in diabetic patients has increased up to 3 folds and it became the major risk for diabetes associated morbidity and mortality. Insulin resistance and oxidative stress both play a ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990372
更新日期:2013-01-01 00:00:00
abstract::Apoptosis is a regulated process leading to cell death, which is implicated both in normal development and in various pathologies including heart failure, stroke and neurodegenerative diseases. Caspase-3, a key enzyme of the apoptotic pathway, is considered as a major target for the treatment of abnormal cell death. M...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795049679
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Cardiovascular disease (CVD) despite the advances in medical management keeps on as the primary cause of morbidity and mortality for both genders in Western societies. Sex differences though modify the clinical picture as well as the effectiveness of treatment. METHODS AND RESULTS:In this literature review ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160606202111
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Bacterial cellulose (BC) has recently attained greater interest in various research fields, including drug delivery for biomedical applications. BC has been studied in the field of drug delivery, such as tablet coating, controlled release systems and prodrug design. OBJECTIVE:In the current work, we tested ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666191011103851
更新日期:2019-01-01 00:00:00
abstract::Drug discovery is generally considered as a costly affair and it takes approximately 15 years to reach a new chemical entity into the market. Among the recent potent drug molecules with most effective pharmacological properties, very few reached for Phase I clinical trial in humans. Unfortunately, the historical avera...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190618121553
更新日期:2019-01-01 00:00:00
abstract::Two morphological features may be seen as a main result of the cardiovascular cell damage caused by cigarette smoking: myocardial cell necrosis and smoke cardiomyopathy that, however, can lead to cell necrosis in case of chronic prolonged exposure to tobacco smoke. Both these pathological patterns recognise hypoxia as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784746699
更新日期:2008-01-01 00:00:00
abstract::Electropulsation (electroporation) is a physical method for delivery of various molecules into the cells in vitro and in vivo. It is an expanding field due to its applicability in cancer therapy, where combined application of electric pulses and chemotherapeutic drugs is used for treatment of cutaneous and subcutaneou...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778559740
更新日期:2006-01-01 00:00:00
abstract::DARPins (designed ankyrin repeat proteins), new kinds of binding proteins, have the potential to overcome the defects of monoclonal antibodies, and hence may become the alternatives to antibodies and generate a novel therapeutic approach. DARPins can be selected to bind any given target proteins with high affinity and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319120017
更新日期:2013-01-01 00:00:00
abstract::Severe acute respiratory syndrome-coronavirus (SARS-CoV-2, or COVID-19 virus) is a worldwide pandemic pathogen infecting 210 territories. It belongs to the family coronaviriadae and the order Nidovirales. The SARS-CoV-2 virus is a positive-sense single-stranded RNA enveloped virus that includes spike proteins projecti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201222162509
更新日期:2020-12-22 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) affects about 20%-30% of the general population, and its clinical relevance arises from the fact that 20%-30% of these subjects develop non-alcoholic steatohepatitis (NASH), a condition at risk of cirrhosis progression. In addition NAFLD, and in particular NASH patients, are al...
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::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::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::BMS-378806 is a prototype of a new class of small molecule HIV-1 inhibitors that blocks viral attachment to cells. This compound exhibits potent inhibitory activity against a panel of HIV-1 laboratory and clinical isolates (M- and T-tropic), selective for HIV-1 and inactive against HIV-2, SIV and a panel of other viru...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384565
更新日期:2004-01-01 00:00:00
abstract::Aquaporins (AQPs) are expressed in physiologically essential tissues and organs in which edema and fluid imbalances are of major concern. Potential roles in brain water homeostasis and edema, angiogenesis, cell migration, development, neuropathological diseases, and cancer suggest that this family of membrane proteins...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782341349
更新日期:2007-01-01 00:00:00
abstract::Melanoma is the deadliest type of skin cancers, accounting for more than 80% of skin cancer mortality. Although melanoma was known very early in the history of medicine, treatment for this disease had remained largely the same until very recently. Previous treatment options, including removal surgery and systemic chem...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200130091318
更新日期:2020-01-01 00:00:00
abstract::Oxidative processes exert a fundamental regulatory function during pregnancy. It depends on the influence of oxygen, nitric oxide, reactive oxygen species and reactive nitrogen species metabolic pathways upon the vascular changes in the maternal organism, as well as on the regulation of uterine and cervical tone throu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054065747
更新日期:2005-01-01 00:00:00
abstract::In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral species, may cause mortality. The discoveries ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612811319060013
更新日期:2013-01-01 00:00:00