Abstract:
:Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and decreased levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the nigrostriatal region of postmortem brains and/or in the ventricular or lumbar cerebrospinal fluid (CSF) from patients with sporadic PD, and in animal models, such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)- and 6-hydroxydopamine (6-OHDA)-induced PD. These changes in cytokine and neurotrophin levels may be initiated by activated microglia, which may then promote apoptotic cell death and subsequent phagocytosis of DA neurons. Cytokines as pleiotropic factors, promote signals that either lead to cell death or exert neuroprotective effects. The discovery of toxic changes in trophic microglia by M. Sawada and co-workers is important to this point. Ultimately, microglial cells may regulate cellular changes that cause either harm or benefit by producing cytokines or neurotrophins depending upon the primary cause and the circumstances during the inflammatory process of PD.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Nagatsu T,Sawada Mdoi
10.2174/1381612053381620subject
Has Abstractpub_date
2005-01-01 00:00:00pages
999-1016issue
8eissn
1381-6128issn
1873-4286journal_volume
11pub_type
杂志文章,评审abstract::The rise of multi-drug resistant and extensively drug resistant M. tuberculosis around the world poses a great threat to human health, and necessitates development of new, effective and inexpensive anti-tubercular agents. The availability of knowledge on molecular biology of M. tuberculosis infection coupled with whol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131118165427
更新日期:2014-01-01 00:00:00
abstract::Glucocorticoids are the first line medication used in the therapy of many severe inflammatory disorders. They exert their activity through binding to the glucocorticoid receptor, a ligand-dependent transcription factor, and result in either activation or repression of a large set of glucocorticoid responsive genes. Th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383610
更新日期:2004-01-01 00:00:00
abstract::After years of pre-clinical and clinical testing monoclonal antibodies (mAbs) finally offer new therapeutic choices for patients with haematological and solid malignancies both as unconjugated antibody and as vectors to target radionuclides in radioimmunotherapy (RIT). In recent years some of the most exciting clinica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399257
更新日期:2000-09-01 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::A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210790883499
更新日期:2010-01-01 00:00:00
abstract:: ...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/1381612825999190515120510
更新日期:2019-01-01 00:00:00
abstract::The need to identify and characterize vulnerable atherosclerotic lesions in humans has lead to the development of various animal models of plaque vulnerability. In this review, current concepts of the vulnerable plaque as it leads to an acute coronary event are described, such as plaque rupture, erosion, intraplaque h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780487575
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the tra...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190705193227
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. OBJECTIVE:The ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200310145935
更新日期:2020-01-01 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:BACKGROUND:Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration. Long non-coding RNAs (lncRNAs) have been associated with inflammatory diseases, including OA. Here, we investigated the potential molecular role of lncRNAs in OA pathogenesis. METHODS:ATDC5 cells were treated with lipopol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190801141801
更新日期:2019-01-01 00:00:00
abstract::Combinations of different technologies are at the heart of the development and implementation of new, innovative processes and approaches for Industry 4.0 in the field of medicinal chemistry and drug discovery. Process intensification and advances in high-throughput synthetic techniques can dramatically improve reacti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826999201116163951
更新日期:2020-01-01 00:00:00
abstract::The drug discovery process in general is a very resource intensive undertaking that has existed for a very long time. In the last two decades, performing molecular simulations that determine the level of interaction between a protein and ligand have been refined to the point where they are now an essential part of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160414142530
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666171227215708
更新日期:2018-01-01 00:00:00
abstract::Oncology remains an increasingly important focus of therapeutic development yet there remain many scientific and operational bottlenecks to deliver optimum treatments efficiently. Radiopharmaceuticals constitute a group of methodologies able to support the many stages of drug development. Methods such as [(18)F]-FDG-P...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787581977
更新日期:2009-01-01 00:00:00
abstract::Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrP(C)) into an isoform designated PrP(Sc). The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrP(C) is a GPI-anchored cell s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698873
更新日期:2006-01-01 00:00:00
abstract::Prostacyclin (PGI(2)) is one of the major vascular protectors against thrombosis and vasoconstriction, caused by thromboxane A(2). Understanding the molecular mechanisms of PGI(2) biosynthesis and signaling is crucial to the development of therapeutic approaches to regulate PGI(2) functions. This review provides infor...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776055994
更新日期:2006-01-01 00:00:00
abstract::Neuregulin1 proteins (NRG1s) are epidermal growth factor (EGF) family members which are ligands for the ErbB receptor tyrosine kinases (RTKs). A decade of research has revealed that the NRG1-ErbB signaling is essential for the cardiac development and pivotal for maintaining the physiological function of the adult hear...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796391010
更新日期:2011-01-01 00:00:00
abstract::In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454748
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Bio-soft material, a class of derivatives of the natural or synthetic material, is getting more and more prevalent in biomedical researches and applications due to the advantages such as in-vivo biodegradation, good water solubility and designable targeting ability. With the presence of bio-sof...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180515154848
更新日期:2018-01-01 00:00:00
abstract::Free energy simulations are a powerful tool to study molecular recognition. The most rigorous variants can provide in depth understanding for a particular system, but are not suited for high throughput application to large libraries of compounds. Related, but less expensive methods are increasingly popular, including ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319230008
更新日期:2013-01-01 00:00:00
abstract::Protein kinases are potential targets of drugs to treat many human diseases. Intensive efforts have been made to develop protein kinase inhibitors, but a major challenge is achieving specificity. Exploiting regulatory elements outside the ATP binding pocket, such as the substrate binding site, may provide an alternati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800672741
更新日期:2012-01-01 00:00:00
abstract::New biopharmaceutical molecules, potentially able to provide more personalized and effective treatments, are being identified through the advent of advanced synthetic biology strategies, sophisticated chemical synthesis approaches, and new analytical methods to assess biological potency. However, translation of many o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151216151420
更新日期:2016-01-01 00:00:00
abstract::The discovery of the delicate role of endogenous nitric oxide in the homeostasis of various cellular functions and the dynamic behaviour of the airways, has led to a new, rapidly progressing area of physiological science, that has direct bearing for our understanding of multiple airway diseases. The potentially protec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778194141
更新日期:2006-01-01 00:00:00
abstract::Doxorubicin has been a constituent of antitumor drug protocols for a broad spectrum of cancers for more than two decades. Side effects and resistance continue to be important limitations. Drug targets responsible for both side effects and anti-tumor activity are cell membrane receptors, cell membrane lipids, nucleic a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:Loss of olfaction can cause noticeable reduction in general quality of life. Only a small portion of patients with olfactory loss respond to current medications. Thus, development of novel therapeutic strategies seems to be necessary. Looking into traditional medical knowledge can be of great value in addres...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170316122949
更新日期:2017-01-01 00:00:00
abstract::In recent years, there has been an exciting focus of research attempting to understand neuropsychiatric disorders from a holistic perspective in order to determine the role of gut microbiota in the aetiology and pathogenesis of such disorders. Thus, the possible therapeutic benefits of targeting gut microbiota are bei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200122153541
更新日期:2020-01-01 00:00:00
abstract::Inflammatory bowel disease (IBD) is a group of disorders characterized by chronic inflammation within the gastrointestinal tract. It is a multifactorial disease associated with immune-cell mediated oxidative damage to the intestinal mucosa. There is no cure for IBD, but anti-cytokine therapy can limit target inflammat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180717110236
更新日期:2018-01-01 00:00:00
abstract::A review of the Electron-Conformational (EC) method of pharmacophore (Pha) identification and quantitative bioactivity prediction in drug design and toxicology is presented, which includes the latest advances and improvements of the method as a whole and details of its realization with illustration of results. In the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454586
更新日期:2003-01-01 00:00:00
abstract::Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (Abeta peptides) in the form of senile plaques as well as neurofibrillary tangles (NFTs) in the brain. In the amyloidogenic pathway, the amyloid-beta precursor protein (APP) is cleaved by beta-secretase first, followed by gamma-se...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778792994
更新日期:2006-01-01 00:00:00